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Dyslipolysis of adipocytes plays a critical role in various diseases. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme in adipocyte autonomous lipolysis. However, the degree of adipocyte lipolysis related to the prognoses in acute pancreatitis (AP) and the role of ATGL-mediated lipolysis in the pathogenesis of AP remain elusive. Herein, the visceral adipose tissue consumption rate in the acute stage was measured in both patients with AP and mouse models. Lipolysis levels and ATGL expression were detected in cerulein-induced AP models. CL316,243, a lipolysis stimulator, and adipose tissue-specific ATGL knockout mice were used to further investigate the role of lipolysis in AP. The ATGL-specific inhibitor, atglistatin, was used in C57Bl/6N and ob/ob AP models. This study indicated that increased visceral adipose tissue consumption rate in the acute phase was independently associated with adverse prognoses in patients with AP, which was validated in mouse AP models. Lipolysis of adipocytes was elevated in AP mice. Stimulation of lipolysis aggravated AP. Genetic blockage of ATGL specifically in adipocytes alleviated the damage to AP. The application of atglistatin effectively protected against AP in both lean and obese mice. These findings demonstrated that ATGL-mediated adipocyte lipolysis exacerbates AP and highlighted the therapeutic potential of ATGL as a drug target for AP., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Importance: Epicardial adipose tissue (EAT) is a biologically active organ surrounding myocardium and coronary arteries that has been associated with coronary artery disease (CAD) and atrial fibrillation. Previous work has shown that EAT exhibits beige features., Objective: Our objective was to determine whether the stromal vascular fraction of the human EAT contains innate or adaptive lymphoid cells compared to thoracic subcutaneous (thSAT), visceral abdominal (VAT) and subcutaneous abdominal (abSAT)., Participants: New pangenomic microarray analysis was performed on previous transcriptomic dataset using significance analysis of microarray and ingenuity pathway analysis (n=41) to identify specific immune signature and its link with browning genes. EAT, thSAT, VAT and abSAT samples from explanted patients with severe cardiomyopathies and multi-organ donor patients (n=17) were used for flow cytometry (FC) immunophenotyping assay. Patients were on average 55±16 years-old; 47% had hypertension and 6% CAD. Phenotypic adaptive and innate immune profiles were performed using a TBNK panel and a specific ILC1-2-3 panel including CD127, CD117, CRTH2 (CD294) and activation markers such as CD25 and CD69., Results: Transcriptomic analysis showed a significant positive correlation between the TH2 immune pathway (IL-4, IL-5, IL-13, IL-25, IL-33) and browning genes (UCP-1, PRDM16, TMEM26, CITED1, TBX1) in EAT versus thSAT (R=0.82, P<0.0001). Regarding adaptive immune cells, a preponderance of CD8T cells, a contingent of CD4T cells, and a few B cells were observed in all ATs (P<0.0001). In innate lymphoid cells (ILCs), an increase was observed in visceral ATs (i.e. EAT; VAT 35±8ILCs/g of tissue) compared to their subcutaneous counterpart (i.e. thSAT+abSAT: 8±3 ILCs/g of AT, P=0.002), with a difference in the proportion of the 3 subtypes of ILCs (ILC1>ILC3>ILC2). In addition, we observed an increase in EAT-ILC2 compared to other ATs and almost all these EAT-ILC2 expressed CD69 and/or CD25 activation markers (99.75±0.16%; P<0.0001). We also observed more NKs in EAT and VAT (1520±71 cells/g of AT) than in SATs (562±17 cells/g of AT); P=0.01., Conclusion: This is the first study to provide a comparison between innate and adaptive lymphoid cells in human epicardial versus abdominal or thoracic adipose tissues. Further studies are ongoing to decipher whether these cells could be involved in EAT beiging., Trial Registration: CODECOH No. DC-2021-4518 The French agency of biomedicine PFS21-005., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Individual patterns of fat accumulation (visceral, subcutaneous, and/or liver fat) can determine cardiometabolic risk profile., Objective: To investigate risk stratification using personalized fat z-scores in persons with a body mass index (BMI) of 30-40 kg/m 2 from the UK Biobank imaging study., Setting: Population-based study., Methods: Whole-body magnetic resonance (MR) images of 40,174 participants from the UK Biobank imaging study were analyzed for visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and liver fat (LF) and used to calculate sex- and body size-invariant fat z-scores (VATz, aSATz, LFz). Associations between z-scores and later incident cardiovascular disease (CVD) and type 2 diabetes (T2D) were investigated using Cox proportional hazards modeling and Kaplan-Meier curves in participants with BMI 30-40 kg/m 2 ., Results: A total of 6716 participants had BMI 30-40 kg/m 2 and within this group, CVD was positively associated with VATz (crude hazard ratio (cHR) [95% CI]: 1.30 [1.20-1.40], P < .001) and negatively associated with aSATz and LFz (cHR: 0.91 [0.85-0.99], P = .028, and 0.88 [0.82-0.95], P = .002). All z-scores remained significant after adjustment for sex, BMI, and age, but only VATz was significant when previous CVD was added. T2D was positively associated with VATz and LFz (cHR: 1.53 [1.40-1.67], P < .001, and 1.35 [1.23-148], P < .001) and negatively associated with aSATz (cHR: 0.90 [0.81-0.99], P = .026). All z-scores remained significant after adjustment for sex, BMI, and age., Conclusions: Personalized MR-derived fat z-scores can identify phenotypes of obesity with specific cardiometabolic risk profiles regardless of BMI. Current guidelines for bariatric surgery based on BMI exclude some of these high-risk patients., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Individuals with a higher abdominal adipose tissue accumulation are at higher risk of developing cardiometabolic diseases. For a given body mass index (BMI), women typically present lower abdominal adipose tissue accumulation compared to men. Whether abdominal adiposity is a causal driver of cardiometabolic risk, or a mere marker of ectopic fat deposition is debated., Methods: We investigated the sex-specific and sex-combined impact of height and BMI-adjusted gluteofemoral adipose tissue (GFATadj) adjusted abdominal subcutaneous adipose tissue (ASATadj) and adjusted visceral adipose tissue (VATadj) on cardiometabolic traits and diseases using Mendelian randomization., Results: Leveraging genome-wide summary statistics on GFATadj, ASATadj and VATadj from 39,076 UK Biobank participants with full-body magnetic resonance imaging available, we found that GFATadj is associated with a more favourable cardiometabolic risk profile including lower low density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, fasting insulin, liver enzyme levels and blood pressure as well as higher high density lipoprotein (HDL) cholesterol levels. GFATadj also is negatively associated with ischemic stroke, coronary artery disease, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). ASATadj is not associated with cardiometabolic traits and diseases, whereas VATadj is associated with liver fat accumulation but not with NAFLD or other cardiometabolic traits or diseases. Although the absolute effect sizes of GFATadj on LDL cholesterol were more pronounced in women compared to men, most associations did not differ by sex., Conclusions: The inability of subcutaneous fat depots to efficiently store energy substrates could be the causal factor underlying the association of visceral lipid deposition with cardiometabolic health., Competing Interests: Declaration of competing interest BJA is a consultant for Novartis, Editas Medicine, Eli Lilly and Silence Therapeutics and has received research contracts from Pfizer, Ionis Pharmaceuticals and Silence Therapeutics. The other authors have nothing to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Obesity in children is related to the development of cardiometabolic complications later in life, where molecular changes of visceral adipose tissue (VAT) and skeletal muscle tissue (SMT) have been proven to be fundamental. The aim of this study is to unveil the gene expression architecture of both tissues in a cohort of Spanish boys with obesity, using a clustering method known as weighted gene co-expression network analysis. For this purpose, we have followed a multi-objective analytic pipeline consisting of three main approaches; identification of gene co-expression clusters associated with childhood obesity, individually in VAT and SMT (intra-tissue, approach I); identification of gene co-expression clusters associated with obesity-metabolic alterations, individually in VAT and SMT (intra-tissue, approach II); and identification of gene co-expression clusters associated with obesity-metabolic alterations simultaneously in VAT and SMT (inter-tissue, approach III). In both tissues, we identified independent and inter-tissue gene co-expression signatures associated with obesity and cardiovascular risk, some of which exceeded multiple-test correction filters. In these signatures, we could identify some central hub genes (e.g., NDUFB8, GUCY1B1, KCNMA1, NPR2, PPP3CC) participating in relevant metabolic pathways exceeding multiple-testing correction filters. We identified the central hub genes PIK3R2, PPP3C and PTPN5 associated with MAPK signaling and insulin resistance terms. This is the first time that these genes have been associated with childhood obesity in both tissues. Therefore, they could be potential novel molecular targets for drugs and health interventions, opening new lines of research on the personalized care in this pathology. This work generates interesting hypotheses about the transcriptomics alterations underlying metabolic health alterations in obesity in the pediatric population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C.M. Aguilera reports financial support was provided by ERDF, Health Institute Carlos III, Spanish Ministry of Science. J. Alcala-Fdez reports financial support was provided by ERDF, Regional Government of Andalusia, Ministry of Economic Transformation, Industry, Knowledge and Universities., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Body fat is stored in anatomically distinct adipose depots that vary in their cell composition and play specialized roles in systemic metabolic homeostasis via secreted products. Their local effects on nearby tissues (e.g. the gut and visceral adipose tissues) are increasingly recognized and this local crosstalk is being elucidated. The major subcutaneous fat depots, abdominal and gluteal-femoral, exert opposite effects on the risk of metabolic disease. The pace of research into developmental, sex, and genetic determinants of human adipose depot growth and function is rapidly accelerating, providing insight into the pathogenesis of metabolic dysfunction in persons with obesity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background & Aims: Computed tomography (CT) scans can measure quantity and distribution of adipose tissue, which are associated with breast cancer prognosis. As a novel prognostic marker, radiodensity of adipose tissue has been examined in multiple cancer types, but never in breast cancer. Lower density indicates larger adipocytes with greater lipid content, whereas higher density can reflect inflammation, fibrosis, vascularity, or even metabolic changes; and both may impact breast cancer prognosis., Methods: We included 2868 nonmetastatic patients with breast cancer diagnosed between January 2005 and December 2013 at Kaiser Permanente Northern California, an integrated healthcare system. From CT scans at diagnosis, we assessed the radiodensity of subcutaneous (SAT) and visceral adipose tissue (VAT) at the third lumbar vertebra and categorized their radiodensity into three levels: low (<1 standard deviation [SD] below the mean), middle (mean ± 1 SD), and high (>1 SD above the mean). Using multivariable Cox proportional hazards regression with adjustment for clinicopathological characteristics including body mass index, we calculated hazard ratios (HRs [95% confidence intervals]) for the associations of adipose tissue radiodensity with overall mortality and breast-cancer-specific mortality., Results: Median age at diagnosis of breast cancer was 56.0 years, most (63.3%) were non-Hispanic White and nearly half (45.6%) were stage II. Compared to middle SAT radiodensity, high SAT radiodensity was significantly associated with increased risk of overall mortality (HR: 1.45 [1.15-1.81]), non-significantly with breast-cancer-specific mortality (HR: 1.32 [0.95-1.84]). Neither low SAT radiodensity nor high or low VAT radiodensity was significantly associated with overall or breast-cancer-specific mortality., Conclusions: High radiodensity of SAT at diagnosis of nonmetastatic breast cancer was associated with increased risk of overall mortality, independent of adiposity and other prognostic factors. Considering both radiodensity and quantity of adipose tissue at different locations could deepen understanding of the role of adiposity in breast cancer survival., Competing Interests: Conflicts of interest Melinda L. Irwin was supported in part by Breast Cancer Research Foundation. Carla M. Prado reported honoraria from Abbott Nutrition, Nestle Health Science, and Fresenius Kabi; and paid consultancy from Nutricia and Pfizer. Others did not claim conflict of interest., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

It has been proposed that direct measurement of adiposity has a greater accuracy as a prognostic factor in various malignancies than anthropometric measures such as BMI. We evaluated the association of visceral and subcutaneous adiposity with outcomes in patients with hematological malignancies with a systematic review and meta-analysis. This systematic review included patients with hematological malignancies who had the analysis of overall mortality and progression-free survival according to their adiposity status. We identified 3137 articles, of which we included seven studies. Patients with visceral low visceral adiposity had 2 times greater mortality risk (HR 2.02, P = .0004) and 80% higher risk of death or disease progression (HR 2.98, P = 0.0002), than patients with normal visceral obesity. Patients classified with subcutaneous adipopenia had almost 3 times greater mortality risk. In conclusion, hematological malignancy patients having low adiposity (subcutaneous or visceral) have worse outcomes., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Recently increasing evidence has suggested that obesity is associated with the development and prognosis of renal cell carcinoma. The aim of the study was to investigate the association between different obesity measurements and overall survival in patients with surgically treated clear cell renal cell carcinoma., Patients and Methods: The data of 342 consecutive patients who underwent radical or partial nephrectomy at Peking University People's Hospital from January 2009 to November 2014 were retrospectively reviewed. Median follow-up was 82 months. The association between different obesity measurements and overall survival was evaluated using the Kaplan-Meier method and Cox regression models., Results: In univariate Cox regression analyses, perirenal fat accumulation was significantly associated with overall survival (HR: 2.271; 95% CI: 1.311-3.935; P = .003), as well as age, sex, clinical manifestation, surgical option, tumor size, and grade. The other obesity measurements, including body mass index, waist circumference, total adipose tissue, visceral adipose tissue, and percentage of visceral adipose tissue, were not assessed as prognostic indicators of overall survival in this study (P > .05). After adjusting for age, sex, clinical manifestation, surgical option, tumor size, T stage, and tumor grade, perirenal fat accumulation was still identified as an independent predictor of overall survival (HR: 2.264; 95% CI: 1.305-3.926; P == .004). The results of Kaplan-Meier model also revealing that patients with higher percentage of perirenal fat showed poorer overall survival (P == .003)., Conclusion: Higher percentage of perirenal adipose tissue is independently associated with increased mortality risk in surgically treated clear cell renal cell carcinoma., Competing Interests: Disclosure None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Body composition has been associated with disease outcome in several cancer types. Results for localized and metastatic renal cell cancer (RCC) are limited and inconsistent. Our aim was to examine the association between body composition and survival in RCC., Methods: We conducted a population-based historical cohort study including patients diagnosed with RCC from 2008 to 2012. Diagnostic Computed Tomography images at the third lumbar vertebra (L3) were assessed for skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI) and subcutaneous adipose tissue index (SATI). Clinical data was retrieved from medical records. Multivariable Cox regressions with restricted cubic splines were used to determine hazard ratios (HRs) and 95% confidence intervals (95%CIs) for 10-unit increases in body composition features with overall survival (OS) and recurrence-free survival (RFS)., Results: We included 719 stage I-III (of whom 254 (35.3%) died and 148 (21.9%) experienced recurrence) and 320 stage IV RCC patients (of whom 298 (93.1%) died). Median follow-up was 6.35 years (interquartile range; 1.41-8.23). For stage I-III, higher SMD was associated with better OS (men: HR 0.86; 95% CI 0.68-1.08; women: HR 0.69; 95% CI 0.50-0.95). Lower compared to median VATI was associated with worse OS for both men (HR 1.38; 95%CI 1.05-1.83 for VATI = 25) and women (HR 1.67; 95%CI 1.01-2.78 for VATI = 20). For stage IV, higher SMD and higher VATI were associated with better OS among men (HR 0.74; 95% CI 0.59-0.94 and HR 0.93; 95% CI 0.88-0.99, respectively). Results for women were similar but non-significant. No statistically significant associations were found for SMI or SATI., Conclusion: Higher SMD and higher VATI were marginally associated with better survival in RCC patients and might be useful for better prognostication. However, the added value to current prognostic scores needs to be investigated., Competing Interests: Conflict of interest All authors declare that they have no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Extracellular vesicles (EVs) have been recently postulated as key players in metabolic disorders emerging as an alternative way of paracrine/endocrine communication. However, the nature of EVs shed by adipose tissue (AT) and their role in obesity is still very limited. Here, we isolated human morbid obese visceral (VAT) and subcutaneous (SAT) whole AT shed EVs from donors submitted to bariatric surgery to characterize their protein cargo by qualitative and quantitative/SWATH mass spectrometry analysis. We identified 574 different proteins shed by morbid obese VAT and 401 proteins in those from SAT, establishing the first obese AT EV proteome reference map. Only 50% of identified proteins in VAT vesicles were common to those in SAT; additionally, EVs shed by obese VAT showed more AT and obesity-related adipokines than SAT. Functional classification shows that obese VAT vesicles exhibit an enrichment of proteins implicated in AT inflammation and insulin resistance such as TGFBI, CAVN1, CD14, mimecan, thrombospondin-1, FABP-4 or AHNAK. Selected candidate biomarkers from the quantitative-SWATH analysis were validated in EVs from independent morbid obese and from moderate obese to lean individuals showing that morbid obese VAT vesicles are characterized by a diminution of syntenin 1 and the elevation of TGFBI and mimecan. Interestingly, TGFBI and mimecan containing vesicles could be detected and quantified at circulating level in plasma. Thus, a significant elevation of -TGFBI-EVs was detected on those obese patients with a history of T2D compared to nondiabetic, and an augmentation of mimecan-EVs in obese plasma compared to those in healthy lean individuals. Thus, we conclude that obese AT release functional EVs carrying AT and obesity candidate biomarkers which vary regarding the AT of origin. Our findings suggest that circulating EV-TGFBI may facilitate monitoring T2D status in obese patients, and EV-mimecan may be useful to track adiposity, and more precisely, visceral obesity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Supervised exercise training improves outcomes in patients with pulmonary arterial hypertension (PAH). The effect of an unsupervised activity intervention has not been tested., Research Question: Can a text-based mobile health intervention increase step counts in patients with PAH?, Study Design and Methods: We performed a randomized, parallel arm, single-blind clinical trial. We randomized patients to usual care or a text message-based intervention for 12 weeks. The intervention arm received three automated text messages per day with real-time step count updates and encouraging messages rooted in behavioral change theory. Individual step targets increased by 20% every 4 weeks. The primary end point was mean week 12 step counts. Secondary end points included the 6-min walk test, quality of life, right ventricular function, and body composition., Results: Among 42 randomized participants, the change in raw steps between baseline and week 12 was higher in the intervention group (1,409 steps [interquartile range, -32 to 2,220] vs -149 steps [interquartile range, -1,010 to 735]; P = .02), which persisted after adjustment for age, sex, baseline step counts, and functional class (model estimated difference, 1,250 steps; P = .03). The intervention arm took a higher average number of steps on all days between days 9 and 84 (P < .05, all days). There was no difference in week 12 six-minute walk distance. Analysis of secondary end points suggested improvements in the emPHasis-10 score (adjusted change, -4.2; P = .046), a reduction in visceral fat volume (adjusted change, -170 mL; P = .023), and nearly significant improvement in tricuspid annular plane systolic excursion (model estimated difference, 1.2 mm; P = .051)., Interpretation: This study demonstrated the feasibility of an automated text message-based intervention to increase physical activity in patients with PAH. Additional studies are warranted to examine the effect of the intervention on clinical outcomes., Clinical Trial Registration: ClinicalTrials.gov; No. NCT03069716; URL: www.clinicaltrials.gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Insulin resistance (IR) is a state when the physiological amount of insulin is not sufficient to evoke proper action, that is, glucose uptake. Numerous conditions lead to IR, including epigenetic components. Epigenetic modifications, associated with obesity and IR are one of the main mechanisms leading to IR pathogenesis. The adipose tissue samples (subcutaneous (SAT) and visceral (VAT)) were collected during abdominal surgery from 40 patients of a wide range of BMI, age, and insulin resistance ratios (F = 9, M = 31). IR was induced in 3T3-L1 adipocytes and human adipocytes collected from SAT and VAT of healthy subjects. Global and site-specific histone modifications (H3K4me3 and H3K9/14ac) were determined. We found lower histone modifications in adipose tissue of IR patients. Furthermore, numerous genes regulating insulin action (PPARG, SLC2A4, ADIPOQ) were differently marked by histone methylation and acetylation. Moreover, we noticed that epigenetic changes appear as soon as 72 h following IR induction. The epigenetic changes appeared to be mediated through the SIRT family. Based on obtained results, the histone marks related to insulin resistance mostly concerned PPARG and SLC2A4 genes. Furthermore, our results proved a vital role of the SIRT family in insulin action and IR pathogenesis., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The physicochemical properties (including morphology, pasting, and thermal properties) of resistant starch (RS) in green banana starch were analyzed after the heat-moisture treatment in the presence of citric acid (CAHMT) at different temperatures. Moreover, this study evaluated whether the administration of CAHMT banana starch could reduce body fat accumulation and modulate gut microbiota. Our results demonstrated that the CAHMT process (90 °C) resulted in a higher retention (80.9%) and thermal stability of RS, alteration in the crystalline structure of starch from B-type to A-type, and increased solubility (27.9-fold) and gelatinization temperatures (from 66.26-78.89 °C to 81.48-92.11 °C). A reduction in swelling power (-57.7%) and a loss of pasting viscosity were also noted. Even after a 30 min boil, the retention rate of residual RS (CAHMT at 90 °C) was up to 50% (4.3-fold higher than the control). Rats fed the CAHMT banana starch resulted in significantly (p < 0.05) lower total visceral fat (-18.1%) and Firmicutes to Bacteroidetes ratio as well as higher total fecal short chain fatty acids. The CAHMT process at 90 °C enhanced the thermal stability of banana RS allowing a wider range of applications in functional foods., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Although visceral fat is strongly correlated with the metabolic complications of obesity, the existing data indicate it is not the cause of these complications. Excess release of free fatty acids (FFA) from adipose tissue lipolysis can account for a sizable portion of the metabolic complications of obesity. In humans, upper-body subcutaneous adipose tissue accounts for most systemic FFA, whereas visceral fat contributes a modest portion of the excess amount to which the liver is exposed. This pattern is maintained in upper-body/visceral obesity, except that greater amounts of visceral fat expose the liver to more FFA from visceral adipose tissue lipolysis., Competing Interests: Disclosure This work was supported by National Institutes of Health Grants DK45343 and DK40484. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: This study was to investigate the degree of susceptibility to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), between the two mice inbred lines C57BL/6N (6N) and C57BL/6J (6J)., Materials and Methods: Four-week old male mice of 6N and 6J substrains (n = 8) were randomized to standard diet (SD) group or high fat (HF) diet group. At the age of 13-week, all two groups of mice were subjected to either air or IH (IH30; thirty hypoxic events per hour) for one week., Key Findings: All mice fed with HF diet exhibited obesity with more body weight and fat mass (percentage to body weight) gain. IH reduced serum LDL, HDL and total cholesterol levels in lean 6J mice. In obese mice, IH lowered obesity-induced serum total cholesterol level in 6J substrain but raised further in 6N substrain. Furthermore, IH caused elevation of serum FFA and MDA levels, and pro-inflammatory cytokines MCP-1 and IL-6 levels in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of lean 6J but not lean 6N mice. There was reduced number of adipocytes and elevation of macrophages in SAT and VAT of HF-induced obese mice of both substrains. IH led to increased number of adipocytes and macrophages in SAT of lean 6J mice., Significance: The genetic difference between 6N and 6J mice may have direct impact on metabolic and inflammatory responses after IH. Therefore, attention must be given for the selection of C57BL mice substrains in the experimental IH-exposed mouse model., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Acute lipolysis of visceral fat or circulating triglycerides may worsen acute pancreatitis (AP)-associated local and systemic injury. The pancreas expresses pancreatic triacylglycerol lipase (PNLIP), pancreatic lipase-related protein 2 (PNLIPRP2), and carboxyl ester lipase (CEL), which may leak into the visceral fat or systemic circulation during pancreatitis. We, thus, aimed to determine the pancreatic lipase(s) regulating lipotoxicity during AP. For this AP, associated fat necrosis was analyzed using Western blot analysis. Bile acid (using liquid chromatography-tandem mass spectrometry) and fatty acid (using gas chromatography) concentrations were measured in human fat necrosis. The fat necrosis milieu was simulated in vitro using glyceryl trilinoleate because linoleic acid is increased in fat necrosis. Bile acid requirements to effectively hydrolyze glyceryl trilinoleate were studied using exogenous or overexpressed lipases. The renal cell line (HEK 293) was used to study lipotoxic injury. Because dual pancreatic lipase knockouts are lethal, exocrine parotid acini lacking lipases were used to verify the results. PNLIP, PNLIPRP2, and CEL were increased in fat necrosis. Although PNLIP and PNLIPRP2 were equipotent in inducing lipolysis and lipotoxic injury, CEL required bile acid concentrations higher than in human fat necrosis. The high bile acid requirements for effective lipolysis make CEL an unlikely mediator of lipotoxic injury in AP. It remains to be explored whether PNLIP or PNLIPRP2 worsens AP severity in vivo., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Biliverdin reductase-A (BVR-A) is a serine/threonine/tyrosine kinase involved in the regulation of insulin signaling. In vitro studies have demonstrated that BVR-A is a substrate of the insulin receptor and regulates IRS1 by avoiding its aberrant activation, and in animal model of obesity the loss of hepatic BVR-A has been associated with glucose/insulin alterations and fatty liver disease. However, no studies exist in humans. Here, we evaluated BVR-A expression levels and activation in peripheral blood mononuclear cells (PBMC) from obese subjects and matched lean controls and we investigated the related molecular alterations of the insulin along with clinical correlates. We showed that BVR-A levels are significantly reduced in obese subjects and associated with a hyper-activation of the IR/IRS1/Akt/GSK-3β/AS160/GLUT4 pathway. Low BVR-A levels also associate with the presence of obesity, metabolic syndrome, NASH and visceral adipose tissue inflammation. These data suggest that the reduction of BVR-A may be responsible for early alterations of the insulin signaling pathway in obesity and in this context may represent a novel molecular target to be investigated for the comprehension of the process of insulin resistance development in obesity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Insulin-like growth factor binding-protein 2 (IGFBP-2) is secreted by differentiating white adipocytes. Clinical studies demonstrate that circulating IGFBP-2 levels associated inversely with body mass index (BMI) and insulin resistance. To explore possible epigenetic changes of the IGFBP2 gene in obesity, we analyzed DNA methylation and mRNA expression in adipocytes from different depots. Healthy lean controls (BMI = 24.5 ± 0.3 kg/m 2 , n = 19) and obese subjects (BMI > 35 kg/m 2 , n = 24) were recruited. All subjects were Swedish Caucasian. Visceral abdominal adipose tissue (VAT) and subcutaneous adipose tissue (SAT) fragments were homogenized. Genomic DNA and total RNAs were extracted. Four CpG sites in the IGFBP2 gene promoter region were analyzed with bisulfite pyrosequencing. IGFBP2 gene expression at mRNA levels was determined with TaqMan real time RT-PCR. Serum samples were used for measurement of circulating IGFBP-2 and leptin levels. IGFBP2 DNA methylation levels in VAT were increased in obese subjects compared with controls (P < .05). By contrast, IGFBP2 mRNA expression levels in VAT were lower in obesity subjects than in controls (P < .05). In SAT, IGFBP2 DNA methylation and RNA expression levels were lower than in VAT, irrespective of obesity. Obese subjects demonstrated increased serum leptin levels (P < .001) and reduced serum IGFBP-2 levels compared to controls (P < .05). In conclusion, the current study demonstrates that IGFBP2 DNA methylation levels are increased in VAT from obese subjects. This suggests that IGFBP-2 is epigenetically regulated in abdominal obesity., (Copyright © 2019. Published by Elsevier Ltd.)

Background: We aimed to further determine the relationship between the areas of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and the ratio of VAT to SAT (VAT/SAT) with the outcomes of acute respiratory distress syndrome (ARDS) patients., Methods: A retrospective study was performed on patients with ARDS in 7 intensive care units (ICU) of West China Hospital, Sichuan University., Results: A total of 169 patients were included in the analysis. Abdominal computed tomography scans of each patient within 24 hours of being admitted to the ICU were assessed by at least 2 investigators. Higher VAT/SAT was related with higher hospital mortality (22% vs. 44%, P = 0.003; adjusted odds ratio [aOR] 0.699, 95% CI 0.530-0.922 ([P = 0.011]). On the contrary, higher SAT and VAT were related to lower hospital mortality in ARDS (aOR 1.077, 95% CI 1.037-1.119 [P < 0.001]; aOR 1.017, 95% CI 1.004-1.030 [P = 0.011], respectively). Patients with higher SAT and VAT had shorter length of ICU stay (ICU LOS) (26.26 vs. 15.83 days, P = 0.031; 25.16 vs. 14.19 days, P = 0.007, respectively), while VAT/SAT was not related with ICU LOS. Moreover, we did not find any significant relationship either between VAT/SAT and mechanical ventilation-free days or between SAT and mechanical ventilation-free days., Conclusions: This study suggests that VAT/SAT can contribute to adverse outcomes of patients with ARDS. However, higher SAT and VAT were related to better prognosis of ARDS patients., (Copyright © 2018. Published by Elsevier Inc.)

Background and Aims: Obese individuals have a higher risk of developing atherosclerosis, possibly driven by adipose tissue (AT) inflammation. We recently showed that AT macrophages (ATMs), which accumulate in the expanding obese AT, produce mediators causing immune cell recruitment from the bone marrow. In the current study, we evaluated whether ATMs are directly involved in atherosclerotic plaque development., Methods: Lean ldlr -/- acceptor mice received visceral AT (vAT) from lean, obese, or ATM-depleted obese ldlr -/- mice. Acceptor mice were fed high cholesterol diet (HCD) for 4 weeks before and 8 weeks after AT transplantation to induce atherosclerosis. Atherosclerotic plaque development was studied 8 weeks after transplantation., Results: Transplanting donor vAT from obese mice increased circulating triglycerides and B-cells, but decreased Ly6c - monocytes. Plasma cholesterol, Ly6c + monocytes, T-cells, NK-cells and eosinophils were unaffected. Depleting ATMs from obese AT using clodronate liposomes prior to vAT transplantation prevented the increase in triglycerides and B-cells and decrease in Ly6c - monocytes, but did increase eosinophils. Circulating Cxcl1 was reduced by obese AT transplantation and Ifn-γ tended to be increased while Tnf and Il-1β were unaffected. ATM-depleted obese AT transplantation also reduced Cxcl1, but increased circulating Tnf levels. However, obese AT transplantation with or without depletion of ATMs did not influence atherosclerotic plaque size, phenotype, or stability., Conclusions: ATMs from obese vAT do not affect atherosclerotic plaque development or phenotype., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: We evaluated the influence of perinephric fat invasion (PFI) compared with sinus fat invasion (SFI) on disease-free survival (DFS) and cancer-specific survival (CSS) after partial nephrectomy (PN) for stage pT3a renal cell carcinoma (RCC)., Materials and Methods: Data were recorded from the consecutive records of patients who had undergone underwent PN for cT1-T2 RCC from 2007 to 2016. Of these patients, 143 had stage pT3a with SFI or PFI found on final pathologic examination. The demographic, perioperative, and pathologic variables were reviewed. DFS and CSS analyses were performed. The factors predicting disease progression in this population were assessed., Results: After a median follow-up period of 28 months (range 15-41 months), 19 patients (13.3%) had developed recurrence, including 5 local and 14 distant metastases, with 11 cancer-specific deaths (7.7%). No differences were found in DFS (5 years, 60.9% vs. 55.3%; log-rank P = .7) or CSS (5 years, 81% vs. 74.2%; log-rank P = .8) between the SFI and PFI groups. For the pT3a fat invasion population, the 2- and 5-year DFS and CSS rates were 83.6% and 58.6% and 93.6% and 78%, respectively. SFI (P = .5) and positive surgical margins (P = .1) did not predict for progression. On multivariate Cox regression, increased tumor size (hazard ratio, 1.5; 95% confidence interval, 1.1-1.9; P < .01) and higher tumor grade (hazard ratio, 3.6; 95% confidence interval, 1.1-4.6; P = .04) were independent predictors of disease progression in the pT3a fat invasion population., Conclusion: In our series of patients with pT3a RCC after PN, SFI compared with PFI was not associated with an increased risk of progression or cancer-specific death., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background & Aims: Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during weight-loss are sparse. We investigated the effect of long-term weight-loss induced intervention diets on dynamics of renal-sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation within the renal parenchyma., Methods: We randomized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets, with or without exercise. We quantified renal-sinus-fat and %renal-parenchymal-fat by whole body magnetic-resonance-imaging., Results: Participants (age = 48 years; 89% men; body-mass-index = 31 kg/m 2 ) had 86% retention to the trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat were directly associated with hypertension, and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for all) after adjustment for body weight. Higher renal-sinus-fat was associated with lower estimated-glomerular-filtration-rate and with higher microalbuminuria and %HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus-fat (-9%; p < 0.05 vs. baseline) but not %renal-parenchymal-fat (-1.7%; p = 0.13 vs. baseline) significantly decreased, and similarly across the intervention groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with weight-loss per-se (p < 0.05). In a model adjusted for age, sex, and visceral-adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with decreased pancreatic, hepatic and cardiac fats (p < 0.05 for all) and with decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (β = 0.13; p = 0.05), triglycerides/HDL-c (β = 0.13; p = 0.05), insulin (β = 0.12; p = 0.05) and gamma glutamyl transpeptidase (β = 0.24; p = 0.001), but not with improved renal function parameters or blood pressure. Decreased intake of sodium was associated with a reduction in %renal-parenchymal-fat, after adjustment for 18 months weight-loss (β = 0.15; p = 0.026) and hypertension (β = 0.14; p = 0.04)., Conclusions: Renal-sinus-fat and renal-parenchymal-fat are fairly related to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic parameters, independent of changes in weight or hepatic fat, rather than with improved renal function or blood pressure parameters. CLINICALTRIALS., Govidentifier: NCT01530724., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Alpha-syntrophin (SNTA) is a molecular adapter protein which is expressed in adipocytes. Knock-down of SNTA in 3T3-L1 preadipocytes increases cell proliferation, and differentiated adipocytes display small lipid droplets. These effects are both characteristics of healthy adipose tissue growth which is associated with metabolic improvements in obesity. To evaluate a role of SNTA in adipose tissue morphology and obesity associated metabolic dysfunction, SNTA deficient mice were fed a standard chow or a high fat diet. Mice deficient of SNTA had less fat mass and smaller adipocytes in obesity when compared to control animals. Accordingly, these animals did not develop liver steatosis and did not store excess triglycerides in skeletal muscle upon high fat diet feeding. SNTA-/- animals were protected from hyperinsulinemia and hepatic insulin resistance. Of note, body-weight, food uptake, and serum lipids were normal in the SNTA null mice. SNTA was induced in adipose tissues but not in the liver of diet induced obese and ob/ob mice. In human subcutaneous and visceral fat of seven patients SNTA was similarly expressed and was not associated with body mass index. Current data demonstrate beneficial effects of SNTA deficiency in obesity which is partly attributed to smaller adipocytes and reduced white adipose tissue mass. Higher SNTA protein in fat depots of obese mice may contribute to adipose tissue hypertrophy and ectopic lipid deposition which has to be confirmed in humans., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Insulin resistance (IR) is an important clinical issue in patients with type 1 diabetes due to worse metabolic control and risk of development of chronic complications., Objective: The aim of the study was to evaluate simple and easily available parameters as indirect markers of IR in adults with type 1 diabetes and correlate it with the results of hyperinsulinemic-euglycemic clamp., Methods: The study included 88 patients (62 men), aged 34.1 ± 6.5 years, with type 1 diabetes with a median disease duration of 8 (7-13) years and mean HbA1c of 7.6 ± 1.5%. Tissue sensitivity to insulin was assessed on the basis of glucose distribution rate (GDR) obtained in the course of hyperinsulinemic-euglycemic clamp. In addition, indirect markers of IR, such as estimated GDR, presence of features of metabolic syndrome, visceral adiposity index (VAI), and the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio, were evaluated., Results: In the study group, IR defined as GDR <4 mg/kg/min was observed in 33 (37.5%) patients. Group with IR had significantly higher postprandial glycemia (9.1 ± 2.0 vs 8.4 ± 1.1 mmol/L, P = .04), serum TG level (1.11 [0.75-1.92] vs 0.85 [0.60-1.08] mmol/L, P = .001), lower HDL-C level (1.59 ± 0.38 vs 1.8 ± 0.5 mmol/L, P = .02), higher TG/HDL-C ratio (1.60 [1.00-3.13] vs 1.05 [0.62-1.53], P = .001), and higher VAI (2.61 [1.31-4.25] vs 1.56 [0.96-2.25], P = .002). Significant relationship between GDR and TG/HDL-C ratio and VAI, adjusted for age, sex, HbA1c, and duration of diabetes was revealed (respectively, odds ratio 1.90 [95% confidence interval 1.15-3.15], P = .01 and odds ratio 1.47 [95% confidence interval 1.06-2.04], P = .01)., Conclusions: TG/HDL-C ratio and VAI appear to be clinically useful tools to assess IR in adults with type 1 diabetes., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements. The measurement of VAT usually implies the use of imaging techniques such as magnetic resonance imaging or computed tomography (CT). Our aim was to evaluate the accuracy of the determination of VAT by means of abdominal bioimpedance (BIA) with the ViScan device in comparison with CT and its clinical usefulness in the management of obesity., Methods: We studied a sample of 140 subjects (73 males/67 females) with BMI ranging from 17.7 to 50.4 kg/m 2 to evaluate the accuracy of the ViScan in comparison to CT to determine VAT. To further analyze ViScan's clinical usefulness we studied a separate cohort (n = 2849) analyzing cardiometabolic risk factors. Furthermore, we studied the ability of the ViScan to detect changes in VAT after weight gain (n = 107) or weight loss (n = 335). The study was performed from October 2009 through June 2015., Results: ViScan determines VAT with a good accuracy in individuals with a CT-VAT up to 200 cm 2 , and then with lower precision with increasing body mass, exhibiting a moderate-high correlation with CT-VAT (r = 0.75, P < 0.001). Importantly, VAT determination with the ViScan exhibits better correlations with several cardiometabolic risk factors such as glucose, triglycerides, HDL-cholesterol and markers of fatty liver than anthropometric measurements such as BMI or waist circumference. ViScan is able to detect VAT variations after body weight changes., Conclusions: Since the possibility of measuring VAT by imaging techniques is not always available, abdominal BIA represents a good alternative to estimate VAT, allowing the identification of patients with increased VAT-related cardiometabolic risk and a better management of obese patients., Trial Registration: ClinicalTrials.gov NCT01055626 and NCT01572090., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Visceral adiposity is of greater risk than obesity in s.c. adipose tissue for diabetes and cardiovascular disease. Its pathogenesis remains unclear, but it is associated with extracellular matrix (ECM) remodeling. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are a family of secreted zinc-dependent metalloproteinases that play crucial roles in development and various diseases because of their ECM remodeling activity. ADAMTS18 is an orphan ADAMTS whose function and substrate remain unclear. Herein, we showed that Adamts18 mRNA was abundantly expressed in visceral (gonadal) white adipose tissue (vWAT) during the early stage of development after birth. Adamts18 knockout (KO) mice showed increased body fat percentage and larger adipocyte size in vWAT relative to wild-type littermates. These findings may be partly attributed to ECM remodeling, especially increased expression of laminin 1 and adipokine thrombospondin 1 in vWAT. Attenuated extracellular signal-regulated kinase 1 and 2 activity, along with increased expression of adipocyte-specific transcription factors peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein β, and marker gene Fabp4, was detected in vWAT of Adamts18 KO mice. Furthermore, Adamts18 KO mice showed early metabolic syndrome, including hyperlipidemia, blood glucose metabolic disorder, and hypertension. ADAMTS18 deficiency promotes atherosclerosis in apolipoprotein E-deficient mice. These results indicate a novel function of ADAMTS18 in vWAT development and associated metabolic disorders., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Growing evidence suggest that macrophage migration inhibitory factor (MIF) plays a vital role in glucose metabolism. We aimed to ascertain whether MIF levels are altered in subjects with prediabetes and also to determine the relationship between MIF and metabolic parameters as well as visceral fat mass., Material and Methods: This cross-sectional study included 40 subjects with prediabetes and 40 age-, body mass index (BMI)- and sex-matched subjects with normal glucose tolerance. Circulating MIF levels were measured using enzyme-linked immunosorbent assay. Metabolic parameters of recruited subjects were evaluated. Visceral fat mass was measured using bioelectrical impedance method., Results: Circulating MIF levels were found to be elevated in subjects with prediabetes compared to controls (26.46 ± 16.98 versus 17.44 ± 11.80 ng/mL, P = 0.007). MIF positively correlated with BMI, visceral fat mass and indirect indices of homeostasis model assessment of insulin resistance. In linear regression model, an independent association was found between MIF levels and metabolic parameters, including BMI, visceral fat mass and homeostasis model assessment of insulin resistance. Multivariate logistic regression analyses revealed that the odds ratio for prediabetes was higher in subjects in the highest quartile of MIF compared to those in the lowest quartile, after adjusting for potential confounders., Conclusions: Increased MIF levels are associated with the elevation of prediabetic risk., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Metabolic surgery is an effective option for treatment of type 2 diabetes. Although body mass index (BMI) has several limitations in differentiating the metabolic risks of the same weight of muscle and fat, it is used as the basis of indication for metabolic surgery., Objectives: Since visceral fat is highly associated with metabolic disease, we evaluated the effectiveness of visceral fat proportion (VFP) for predicting metabolic risk preoperatively., Setting: University hospital., Methods: Fifty-two type 2 diabetes patients with BMI≤35 kg/cm 2 who underwent gastrectomy for gastric cancer were included. Pre- and postoperative VFPs were measured using abdominal computed tomography. Multivariate logistic regression analysis was performed to estimate the effect of VFP on type 2 diabetes. Receiver operating curve analysis was used to estimate the effectiveness of VFP as a predictor of type 2 diabetes improvement., Results: Thirty-three of the 52 patients (63%) showed improved type 2 diabetes postoperatively. Low preoperative VFP (odds ratio [OR] = .913; 95% confidence interval [CI] = .835-.999; P = .048) and low glycated hemoglobin level (OR = .357; 95% CI = .172-.742; P = .006) were associated with type 2 diabetes improvement 2 years after gastrectomy. The area under the curve was 70.2%, indicating moderate accuracy., Conclusions: Preoperative VFP might be a reasonable predictive factor for type 2 diabetes improvement after gastrectomy for patients with a BMI≤35 kg/cm 2 . High-quality studies of visceral fat for metabolic function are needed in the future., (Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

A genetic influence on methylation levels has been reported and methylation quantitative trait loci (meQTL) have been identified in various tissues. The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. To pinpoint candidate genes for testing the association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. A genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites. The genome-wide association study conducted to identify the SNPs (meQTL) associated with methylation levels at variable CpG sites revealed 2292 significant associations (P < 2.22 × 10 -11 ) involving 2182 unique meQTLs regulating the methylation levels of 174 variable CpG sites. Two meQTLs disrupting CpG sites located within the collagen-encoding COL11A2 gene were tested for associations with MetS and its components in a cohort of 3021 obese individuals. Rare alleles of these meQTLs showed association with plasma fasting glucose levels. Further analysis conducted on these meQTL suggested a biological impact mediated through the disruption of transcription factor (TF)-binding sites based on the prediction of TF-binding affinities. The current study identified meQTL in the VAT of severely obese men and revealed associations of two COL11A2 meQTL with fasting glucose levels., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background & Aim: During cancer development, fat loss occurs in most cancer patients. Characterization of the behavior of fat loss from visceral (VAT) and subcutaneous adipose tissue (SAT) depots has not been established. The first objective of this study was to assess the intensity and time course of changes in VAT and SAT depots of advanced cancer patients in the year preceding death. Secondly, this study explored the differences in adipokine content and fatty acid composition between VAT and SAT depots and in relation to changes in fat mass., Methods: Longitudinal quantitative analyses of computed tomography images was conducted to define changes in adipose tissue cross sectional areas in fat depots in advanced colorectal and cholangiocarcinoma cancer patients (n = 46) at mean time points corresponding to 9, 6, 3 and 1 month before death. Proportions of adipose tissue fatty acid and adipokine content were characterized in a second cohort of advanced colorectal cancer patients (n = 16)., Results: On average, loss of total adipose tissue (TAT) happens at all time intervals but there is an elevation in the intensity of loss close to death. Nine months from death, 42% of patients were losing fat (Mean TAT cross sectional area change = -0.2 ± 13 cm 2 ) whereas within one month from death, fat wasting was observed in 78% of patients (-60.1 ± 9.2 cm 2 , P = 0.001). However, loss of TAT did not reflect changes in VAT and SAT in the same direction or intensity. Intensity of VAT loss remains constant throughout the disease progression whereas SAT is more likely to be gained further way from death. Nine month prior to death, mean change in cross sectional area of VAT was -7.9 ± 6.8 cm 2 whereas, mean change in CSA of SAT was 7.4 ± 7.7 cm 2 (p = 0.03). One month before death, mean VAT and SAT absolute changes were -24.5 ± 4.9 cm 2 and -34.5 ± 5.2 cm 2 , respectively (p = 0.05). Moreover, fat losing patients had higher proportions of polyunsaturated fatty acids, especially n-6 fatty acids, in VAT compared to patients who were gaining fat (mean = 15.4% in losing group vs. 13.4% in gaining group; p = 0.03). VAT contained more monocyte chemoattractant protein-1 than SAT, whereas leptin levels were higher in SAT., Conclusions: Further from death, VAT and SAT behave differently whereas close to death, accelerated loss occurs in both depots. These differences are further characterized by differences in fatty acid composition and adipokine levels., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Roux-en-Y gastric bypass (RYGB) is an effective treatment for patients with type 2 diabetes (T2D) and morbid obesity. However, T2D remission after surgery has not been adequately studied in Chinese patients with a body mass index (BMI)<30 kg/m 2 ., Objectives: The objective of this study was to evaluate the 3-year effect of RYGB among patients with T2D with a BMI<30 kg/m 2 and elucidate the predictors of T2D remission., Setting: Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China., Methods: Sixty-six Chinese patients with T2D and a BMI 25-30 kg/m 2 were retrospectively examined for metabolic outcomes 3 years after RYGB. Remission was defined as glycated hemoglobin (HbA1C)<6.5% and no medications. Binary logistic regression analysis was used to identify preoperative parameters independently predictive of diabetes remission at 1 and 3 years postoperatively [variables: sex, age, BMI, T2D duration, plasma glucose 2 hours after meal, HbA1C, fasting C-peptide, visceral fat area, free triiodothyronine, and thyroid-stimulating hormone. There was no significant difference in fasting insulin or glucose between the remission and no remission groups., Results: Patients were a mean 50.4±11.4 years of age at baseline, and 57.6% were female. Mean T2D duration was 8.9±5.2 years, baseline HbA1C level was 8.3±1.9%, and baseline BMI was 28.2±1.2 kg/m 2 (range: 25.5-30.0). BMI was 22.5±1.8 kg/m 2 (range: 19.1-28.0) at 1 year and 23.0±1.76 kg/m 2 (range: 19.7-28.0) at 3 years. Remission was achieved in 49 patients (74.2%) at 1 year and 38 patients (57.6%) at 3 years. There was a significant reduction in medication for diabetes, hypertension, and hyperlipidemia (P<.01). Compared with patients in the no remission group, patients in the remission group had higher fasting C-peptide levels (P<.01) and free triiodothyronine levels (P = .01) at 1 year. Multiple logistic regression analysis confirmed that fasting C-peptide (odds ratio = 3.795, P = .007) and free triiodothyronine (odds ratio = 4.661, P = .019) levels were predictors of T2D remission at 1 year. No significant difference was found between the 2 groups at 3 years., Conclusions: RYGB resulted in significant clinical and biochemical improvements in Chinese patients with BMI 25-30 kg/m 2 and T2D. Appropriate patient selection (better β-cell function) may produce better outcomes., (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The relationship of lipoprotein particle subclasses to visceral adipose tissue area (VAT-area) in obese children has not been examined previously., Objectives: The study aims were to compare the relationships of VAT-area, homeostatic model assessment of insulin resistance (HOMA-IR), and body mass index (BMI) with lipids and lipoprotein subclasses in obese adolescents and to determine whether these relationships vary by sex., Methods: This cross-sectional study of obese adolescents (BMI ≥ 95th percentile), aged 12 to 18 years, measured VAT-area by dual-energy X-ray absorptiometry, BMI, fasting lipids, lipoprotein subclasses, and HOMA-IR. Linear regression models evaluated the associations of VAT-area, HOMA-IR, and BMI with lipid cardiometabolic risk factors. Sex-stratified analyses further explored these associations., Results: Included were 127 adolescents (age = 14.4 ± 1.5 years; 53.5% female; 88.2% African-American), mean BMI = 34.0 ± 5.1 kg/m(2). VAT-area was negatively associated with low-density lipoprotein particle (LDL-P) size (β = -0.28, P = .0001), high-density lipoprotein particle (HDL-P) size (β = -0.33, P < .0001), and large HDL-P concentration (β = -0.29, P < .0001) and positively associated with small LDL-P concentration (β = 0.23, P = .0005) and small HDL-P concentration (β = 0.25, P = .05). When VAT-area, HOMA-IR, and BMI associations were compared, VAT-area had the strongest associations with most of the lipoprotein subclasses. After sex stratification, the associations of VAT-area with HDL cholesterol, LDL-P size, and large LDL-P concentration were significant only for females (all P < .05)., Conclusions: In a cohort of largely African-American obese adolescents, VAT-area was associated with a more atherogenic lipoprotein subclass profile. When compared with HOMA-IR and BMI, VAT-area had the strongest associations with most lipoprotein subclasses. The relationships between VAT-area and certain lipoprotein subclasses are significantly different in males vs females., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Associations between demographic data and arterial stiffness have not been examined adequately in Chinese obese patients with type 2 diabetes (T2DM) who underwent Roux-en-Y gastric bypass (RYGB)., Objective: This study was designed to examine changes in body fat distribution and metabolic parameters after RYGB and whether these changes correlated with improved arterial stiffness., Setting: The study was performed at the authors' academic university-affiliated hospital., Methods: A retrospective review of 42 Chinese patients with a diagnosis of obesity and T2DM and 22 health controls was conducted, focusing on metabolic outcomes and aortic pulse wave velocity (PWV) before and 12 months after RYGB., Results: At baseline, PWV in the study group was significantly greater than in the control group (6.9±1.5 versus 5.8±.6 ms, respectively; P<.01). PWV was negatively correlated with age, systolic blood pressure, diastolic blood pressure, visceral fat area (VFA), and leptin level (r = .47, P<.01; r = .39, P<.01; r = .31, P = .03; r = .47, P<.01; and r = .30, P = .03, respectively). Multiple stepwise regression found that age and VFA were independently associated with PWV (β = .40, P<.01; β = .30, P = .02, respectively). PWV, body mass index, VFA, and metabolic profiles all improved significantly 12 months after RYGB. The change in PWV was positively correlated with changes in VFA and the leptin level (r = .40, P = .03; r = .40, P = .02, respectively)., Conclusions: Decreased VFA resulting from RYGB correlated with improved arterial stiffness in obese Chinese patients with T2DM. Leptin might be an important factor linking PWV and visceral fat accumulation., (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Previous studies indicate that epicardial adipose tissue (EAT) biologically contributes to the progression of coronary atherosclerosis. We evaluated the relationship between EAT pathology, represented by inflammation and neoangiogenesis, and coronary atherosclerosis on computed tomography (CT) images., Methods: We performed CT examination in 45 patients scheduled for cardiac surgery (coronary artery bypass graft [CABG], n = 21; non-CABG, n = 24) to assess visceral adipose tissue (VAT) area, EAT volume, coronary calcium score (CCS), and presence of non-calcified coronary plaque (NCP) on CT angiography. Each patient was assessed with the numbers of CD68(+) individual macrophages and CD31(+) neovessels in six random high-power fields (400×) of EAT samples subsequently obtained during cardiac surgery., Results: In three groups based on CCS (mild, 0-100; moderate, 101-400; severe, >400), the moderate group had the most extensive macrophage infiltration (p = 0.0025) and neoangiogenesis (p = 0.0036) in EAT. The patients with NCP had more extensive macrophage infiltration (p = 0.010) and neoangiogenesis (p = 0.0043) in EAT than those without. On multivariate analysis adjusted for age, sex, CABG versus. non-CABG, VAT area, and EAT volume, moderate CCS and the presence of NCP showed significant correlations with increased macrophage infiltration (β = 0.65; p < 0.0001, and β = 0.49; p = 0.0089, respectively) and neoangiogenesis (β = 0.55; p = 0.0011, and β = 0.53; p = 0.012, respectively) in EAT., Conclusion: Inflammation and neoangiogenesis in EAT independently correlate with moderate coronary calcification and presence of NCP, suggesting that these two factors may have a role in promoting coronary atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Occurrence of oxidative stress in white adipose tissues contributes to its dysfunction and the development of obesity-related metabolic complications. Coenzyme Q10 (CoQ10) is the single lipophilic antioxidant synthesized in humans and is essential for electron transport during mitochondrial respiration. To understand the role of CoQ10 in adipose tissue physiology and dysfunction, the abundance of the oxidized and reduced (CoQ10red) isoforms of the CoQ10 were quantified in subcutaneous and omental adipose tissues of women covering the full range of BMI (from 21.5 to 53.2 kg/m(2)). Lean women displayed regional variations of CoQ10 redox state between the omental and subcutaneous depot, despite similar total content. Obese women had reduced CoQ10red concentrations in the omental depot, leading to increased CoQ10 redox state and higher levels of lipid hydroperoxide. Women with low omental CoQ10 content had greater visceral and subcutaneous adiposity, increased omental adipocyte diameter, and higher circulating interleukin-6 and C-reactive protein levels and were more insulin resistant. The associations between abdominal obesity-related cardiometabolic risk factors and CoQ10 content in the omental depot were abolished after adjustment for omental adipocyte diameter. This study shows that hypertrophic remodeling of visceral fat closely relates to depletion of CoQ10, lipid peroxidation, and inflammation., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)

Background and Aim: Epicardial and pericardial fat are well-established surrogate markers of cardiovascular diseases and complications. Extra-media thickness (EMT) is a novel ultrasound index corresponding to arterial adventitia and adipose tissue. We aimed to evaluate the association between carotid EMT and epicardial fat (EF) and pericardial fat (PF) and their relation to cardiovascular risk and metabolic syndrome (MS)., Methods and Results: One hundred consecutive patients (age: 51.7 ± 15.4 years; males 70%) scheduled for cardiac magnetic resonance (CMR) were prospectively included in the study. Anthropometric parameters, CMR indices of EF and PF, both common carotid arteries EMT, and ultrasound indices of visceral and subcutaneous fat were measured in patients. In our study group, 53% of patients represented a very high cardiovascular risk, overweight or obesity was found in 68%, high body fat in 45%, and MS in 59% of individuals. Mean EMT (662 ± 129 μm) was significantly associated with EF area (r = 0.46; p < 0.001) and PF area (r = 0.3; p < 0.001). Among all fat indices, only EMT (MS+ 736 ± 140 μm vs. MS-658 ± 97 μm; p = 0.002) and EF area (MS+ 870 ± 451 mm(2) vs. MS 668 ± 333 mm(2); p = 0.02) were significantly increased in patients with MS compared with individuals without MS. Multivariable regression analysis also showed that mean EMT is independently associated with number of cardiovascular risk factors (b = 0.005; p < 0.001). Moreover, very high cardiovascular risk subjects showed significantly increased EMT/BMI (p < 0.001) and EF area/BMI (p = 0.03) ratios. However, there was no significant association between EMT/BMI and EF area/BMI values (p = ns)., Conclusions: Our study showed the first findings on the relations between a novel ultrasound index EMT and EF assessed in a reference method of CMR. Carotid EMT may be a new surrogate marker, including both periarterial fat as a major component and arterial adventitia, which may provide additional data on cardiometabolic risk beyond that derived form a well-established EF alone., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Both overall and abdominal adiposity are established risk factors for cardiovascular disease. Visceral adipose tissue (VAT) and total body fat (TBF) are strongly correlated and previous studies did not make this distinction., Objective: We aimed to distinguish individual contributions of TBF, VAT, and the ratio of VAT to abdominal subcutaneous adipose tissue (VAT/SAT) to subclinical atherosclerosis in men and women., Methods: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity (NEO) study, we assessed VAT and SAT with magnetic resonance imaging, TBF with bio-electrical impendence analysis, and carotid Intima-Media Thickness (cIMT) with ultrasound. We performed linear regression analyses of standardized values of TBF, VAT, VAT/SAT with cIMT. We adjusted the models for confounding factors (age, sex, ethnicity, education, smoking, alcohol, physical activity), and either for VAT or TBF., Results: This analysis included 2451 participants, 53% men with mean (SD) cIMT of 615 (91)μm. After adjustment for confounding factors, the difference in cIMT (95% CI) per SD in VAT was 14 (8,21)μm in men and 18 (13,24)μm in women. After adjustment for TBF, this attenuated to 5 (-3,13)μm in men and 13 (5,20)μm in women. In the full model, differences in cIMT (95% CI) per SD of TBF were 14 (6,22)μm in men and 8 (0,16)μm in women, and per SD of VAT/SAT were 7 (-1,15)μm and 9 (3,16)μm respectively., Conclusions: In this population-based study, VAT contributed beyond overall adiposity to subclinical atherosclerosis, particularly in women. This implies a specific role of VAT in the early development of atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions., Objectives: Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed., Design: Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips., Results: Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage., Conclusions: As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer., (© 2015 American Society for Nutrition.)

Background and Aims: Very little information is available on whether docosahexaenoic acid (DHA) supplementation has a beneficial effect on liver fat and cardiovascular disease (CVD) risk factors in children with nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled randomized trial we investigated whether 6-month treatment with DHA improves hepatic fat and other fat depots, and their associated CVD risk factors in children with biopsy-proven NAFLD., Methods and Results: Of 58 randomized children, 51 (25 DHA, 26 placebo) completed the study. The main outcome was the change in hepatic fat fraction as estimated by magnetic resonance imaging. Secondary outcomes were changes in visceral adipose tissue (VAT), epicardial adipose tissue (EAT), and left ventricular (LV) function, as well as alanine aminotransferase (ALT), triglycerides, body mass index-standard deviation score (BMI-SDS), and insulin sensitivity. At 6 months, the liver fat was reduced by 53.4% (95% CI, 33.4-73.4) in the DHA group, as compared with 22.6% (6.2-39.0) in the placebo group (P = 0.040 for the comparison between the two groups). Likewise, in the DHA group VAT and EAT were reduced by 7.8% (0-18.3) and 14.2% (0-28.2%), as compared with 2.2% (0-8.1) and 1.7% (0-6.8%) in the placebo group, respectively (P = 0.01 for both comparisons). There were no significant between-group changes for LV function as well as BMI-SDS and ALT, while fasting insulin and triglycerides significantly decreased in the DHA-treated children (P = 0.028 and P = 0.041, respectively)., Conclusions: DHA supplementation decreases liver and visceral fat, and ameliorates metabolic abnormalities in children with NAFLD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Aims: Visceral fat (VF) is a source of pro-inflammatory adipokines implicated in cardiac remodeling. We sought to determine the impact of visceral fat and subcutaneous fat (SQ) depots on left ventricular (LV) structure, function, and geometry in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods and Results: We performed a post-hoc analysis on 1151 participants from MESA with cardiac magnetic resonance quantification of LV mass and LV mass-to-volume ratio (LVMV, an index of concentricity) and computed tomographic-derived SQ and VF area. Multivariable regression models to estimate association between height-indexed SQ and VF area (per cm(2)/m) with height-indexed LV mass (per height(2.7)) and LVMV were constructed, adjusted for clinical, biochemical, and demographic covariates. We found that both VF and SQ area were associated with height-indexed LV mass (ρ = 0.36 and 0.12, P < 0.0001, respectively), while only VF area was associated with LVMV (ρ = 0.28, P < 0.0001). Individuals with above-median VF had lower LV ejection fraction, greater indexed LV volumes and mass, and higher LVMV (all P < 0.001). In multivariable models adjusted for weight, VF (but not SQ) area was associated with LV concentricity and LV mass index, across both sexes., Conclusion: Visceral adiposity is independently associated with LV concentricity, a precursor to heart failure. Further study into the role of VF in LV remodeling as a potential therapeutic target is warranted., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background & Aims: Aerobic exercise reduces liver fat and visceral adipose tissue (VAT). However, there is limited data from randomized trials to inform exercise programming recommendations. This study examined the efficacy of commonly prescribed exercise doses for reducing liver fat and VAT using a randomized placebo-controlled design., Methods: Inactive and overweight/obese adults received 8 weeks of either; i) low to moderate intensity, high volume aerobic exercise (LO:HI, 50% VO 2peak, 60 min, 4d/week); ii) high intensity, low volume aerobic exercise (HI:LO, 70% VO 2peak, 45 min, 3d/week); iii) low to moderate intensity, low volume aerobic exercise (LO:LO, 50% VO 2peak, 45 min, 3d/week); or iv) placebo (PLA). Liver fat (spectroscopy) and VAT (magnetic resonance imaging) were measured before and after intervention., Results: Forty-seven of the 48 (n = 12 in each group) participants completed the trial. There were no serious adverse events. There was a significant change in group × time interaction in liver fat, which reduced in HI:LO by 2.38 ± 0.73%, in LO:HI by 2.62 ± 1.00%, and in LO:LO by 0.84 ± 0.47% but not in PLA (increase of 1.10 ± 0.62%) (p = 0.04). There was a significant reduction in VAT in HI:LO (-258.38 ± 87.78 cm(3)), in LO:HI (-386.80 ± 119.5 cm(3)), and in LO:LO (-212.96 ± 105.54 cm(3)), but not in PLA (92.64 ± 83.46 cm(3)) (p = 0.03). There were no significant differences between the dose or intensity of the exercise regimen and reductions in liver fat or VAT (p > 0.05)., Conclusion: The study found no difference in efficacy of liver fat reduction by either aerobic exercise dose or intensity. All of the aerobic exercise regimens employed reduced liver fat and VAT by a small amount without clinically significant weight loss., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Impaired mitochondrial function is important in obesity and the development of insulin resistance and diabetes. The aim of this study was to identify human adipocyte-derived mitochondrial proteins associated with obesity. Mitochondrial proteins from 20 abdominal omental adipose tissue biopsies (13 obese and 7 control subjects) were separated by anion-exchange chromatography coupled to SDS-PAGE. Protein contents were compared and identified by MALDI-TOF-TOF mass spectrometry. Proteins of interest were validated, verified and quantified using immuno dot blot assays in a total of 76 mitochondrial preparations from both obese and non-obese patients. Mass spectrometric comparison of 20 mitochondrial proteomes yielded 62 proteins that were differentially expressed in adipose tissue of obese subjects. The immunological quantification of 12 mitochondrial proteins from 76 omental adipose tissue biopsies revealed four proteins, citrate synthase, HADHA, LETM1 and mitofilin inversely being associated with BMI, and mitofilin being inversely correlated with gender., Biological Significance: The finding that obese human subjects have reduced levels of important mitochondrial proteins in adipocytes of omental adipose tissue as compared to non-obese controls gives new insights in the impairment of mitochondrial function in this specialized compartment of human adipose tissue in obesity and may eventually lead to the definition of valuable obesity markers., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Aims: The relation between adiposity and arterial stiffness remains controversial. We determined whether abdominal and visceral adipose tissue may be a better predictor of arterial stiffness than general obesity in middle-aged adults., Methods and Results: A total of 146 participants (76 men, 70 women; 50 years) were studied. The automatic vascular screening device (Omron VP-1000plus) was used to measure blood pressure simultaneously in the arms and ankles and to determine arterial stiffness by pulse wave velocity (PWV). Using multiple linear regressions, the relations between indicators of obesity and arterial stiffness were examined after adjustment for confounders. Both carotid-femoral PWV and brachial-ankle PWV were significantly associated with BMI (both P < 0.05) but not with body fat percentage. Measures of abdominal obesity, including waist circumference and visceral fat mass (via DXA), were strongly associated with PWV and remained positively associated with arterial stiffness after adjustment for age and gender. Cardiovascular fitness as assessed by maximal oxygen consumption was related to body fat percentage but not with visceral fat. More favorable cardiovascular health profile was associated with both lower visceral fat mass and PWV (both P < 0.001)., Conclusion: Abdominal obesity and visceral fat are associated with large artery stiffness. These findings support the importance of adiposity measures as a risk factor for arterial stiffening in middle-aged adults., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background & Aims: Lieber-DeCarli diet has been used to induce obesity and non-alcoholic steatohepatitis (NASH). As scarce anatomical and clinical-related information on this diet model exists and being exercise an advised strategy to counteract metabolic diseases, we aimed to analyze the preventive (voluntary physical activity - VPA) and therapeutic (endurance training - ET) effect of exercise on clinical/anatomical features of rats fed with Lieber-DeCarli diet., Methods: In the beginning of the protocol, Sprague-Dawley rats were divided into standard-diet sedentary (SS, n = 20), standard-diet VPA (SVPA, n = 10), high-fat diet sedentary (HS, n = 20) and high-fat diet VPA (HVPA, n = 10) groups. After 9-weeks, half (n = 10) of SS and HS groups were engaged in an ET program (8 wks/5 d/wk/60 min/day). At this time, a blood sample was collected for biochemical analysis. At the end of protocol (17-weeks) anatomic measures were assessed. Heart, liver, femur and visceral fat were weighted and blood was collected again. Liver section was used for histopathological examination., Results: At 17-weeks, high-fat diet increased visceral adiposity (HS vs. SS), which was counteracted by both exercises. However, ET was the only intervention able to diminished obesity-related measures and the histological features of NASH. Moreover, blood analysis at 9 weeks showed that high-fat diet increased ALT, AST, cholesterol and HDL while VLDL and TG levels were decreased (HS vs. SS). Notably, although these parameters were counteracted after 9-weeks of VPA, they were transitory and not observed after 17-weeks., Conclusions: ET used as a therapeutic tool mitigated the clinical/anatomical-related features induced by Liber-DeCarli diet, thus possibly contributing to control obesity and metabolic disorders., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Increased visceral adipose tissue (VAT) is associated with reductions in endogenous GH secretion, possibly as a result of hyperinsulinemia, increased circulating free fatty acid, increased somatostatin tone, and reduced ghrelin. Reduced GH may, in turn, further exacerbate visceral fat accumulation because of decreased hormone-sensitive lipolysis in this depot. Data from multiple populations demonstrate that both reduced GH and increased VAT appear to contribute independently to dyslipidemia, increased systemic inflammation, and increased cardiovascular risk. The reductions in GH in states of visceral adiposity are characterized by reduced basal and pulsatile GH secretion with intact pulse frequency. Treatment with GH-releasing hormone (GHRH) provides a means to reverse these abnormalities, increasing endogenous basal and pulsatile GH secretion without altering pulse frequency. This review describes data from HIV-infected individuals and individuals with general obesity showing that treatment with GHRH significantly reduces visceral fat, ameliorates dyslipidemia, and reduces markers of cardiovascular risk. Further research is needed regarding the long-term efficacy and safety of this treatment modality., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Visceral fat necrosis has been associated with severe acute pancreatitis (SAP) for over 100 years; however, its pathogenesis and role in SAP outcomes are poorly understood. Based on recent work suggesting that pancreatic fat lipolysis plays an important role in SAP, we evaluated the role of pancreatic lipases in SAP-associated visceral fat necrosis, the inflammatory response, local injury, and outcomes of acute pancreatitis (AP). For this, cerulein pancreatitis was induced in lean and obese mice, alone or with the lipase inhibitor orlistat and parameters of AP induction (serum amylase and lipase), fat necrosis, pancreatic necrosis, and multisystem organ failure, and inflammatory response were assessed. Pancreatic lipases were measured in fat necrosis and were overexpressed in 3T3-L1 cells. We noted obesity to convert mild cerulein AP to SAP with greater cytokines, unsaturated fatty acids (UFAs), and multisystem organ failure, and 100% mortality without affecting AP induction or pancreatic necrosis. Increased pancreatic lipase amounts and activity were noted in the extensive visceral fat necrosis of dying obese mice. Lipase inhibition reduced fat necrosis, UFAs, organ failure, and mortality but not the parameters of AP induction. Pancreatic lipase expression increased lipolysis in 3T3-L1 cells. We conclude that UFAs generated via lipolysis of visceral fat by pancreatic lipases convert mild AP to SAP independent of pancreatic necrosis and the inflammatory response., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Adipocyte hypertrophy and hyperplasia have been shown to be associated with shorter telomere length, which may reflect aging, altered cell proliferation and adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat distribution and AT cellular composition may contribute to obesity related metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are different between: (1) abdominal subcutaneous and omental fat depots, (2) superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and cells of the stromal vascular fraction (SVF). We further asked whether AT TL is related to age, anthropometric and metabolic traits. TL was analyzed by quantitative PCR in total human genomic DNA isolated from paired subcutaneous and visceral AT of 47 lean and 50 obese individuals. In subgroups, we analyzed TL in isolated small and large adipocytes and SVF cells. We find significantly shorter TL in subcutaneous compared to visceral AT (P < 0.001) which is consistent in men and subgroups of lean and obese, and individuals with or without type 2 diabetes (T2D). Shorter TL in SAT is entirely due to shorter TL in the SVF compared to visceral AT (P < 0.01). SAT TL is most strongly correlated with age (r = -0.205, P < 0.05) and independently of age with HbA1c (r = -0.5, P < 0.05). We found significant TL differences between superficial SAT of lean and obese as well as between individuals with our without T2D, but not between the two layers of SAT. Our data indicate that fat depot differences in TL mainly reflect shorter TL of SVF cells. In addition, we found an age and BMI-independent relationship between shorter TL and HbA1c suggesting that chronic hyperglycemia may impair the regenerative capacity of AT more strongly than obesity alone., (Copyright © 2015 Elsevier Inc. All rights reserved.)