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Purpose To assess adherence to the US Liver Imaging Reporting and Data System (LI-RADS) recommendations for hepatocellular carcinoma (HCC) surveillance and associated patient-level factors in a vulnerable, diverse patient sample. Materials and Methods The radiology report database was queried retrospectively for patients who underwent US LI-RADS-based surveillance examinations at a single institution between June 1, 2020, and February 28, 2021. Initial US and follow-up liver imaging were included. Sociodemographic and clinical data were captured from electronic medical records. Adherence to radiologist recommendation was defined as imaging (US, CT, or MRI) follow-up in 5-7 months for US-1, imaging follow-up in 3-6 months for US-2, and CT or MRI follow-up in 2 months for US-3. Descriptive analysis and multivariable modeling that adjusted for age, sex, race, and time since COVID-19 pandemic onset were performed. Results Among 936 patients, the mean age was 59.1 years; 531 patients (56.7%) were male and 544 (58.1%) were Asian or Pacific Islander, 91 (9.7%) were Black, 129 (13.8%) were Hispanic, 147 (15.7%) were White, and 25 (2.7%) self-reported as other race. The overall adherence rate was 38.8% (95% CI: 35.7, 41.9). The most common liver disease etiology was hepatitis B (60.6% [657 of 936 patients]); 19.7% of patients (183 of 936) had current or past substance use disorder, and 44.8% (416 of 936) smoked. At adjusted multivariable analysis, older age (odds ratio [OR], 1.20; P = .02), male sex (OR, 1.62; P = .003), hepatology clinic attendance (OR, 3.81; P < .001), and recent prior US examination (OR, 2.44; P < .001) were associated with full adherence, while current smoking (OR, 0.39; P < .001) was negatively associated. Conclusion Adherence to HCC imaging surveillance was suboptimal, despite US LI-RADS implementation. Keywords: Liver, Ultrasound, Screening, Abdomen/GI, Cirrhosis, Metabolic Disorders, Socioeconomic Issues Supplemental material is available for this article. © RSNA, 2024.

Background: China has undergone a significant socioeconomic transformation over the past few decades due to the implementation of family planning policies. These societal changes have resulted in an increased susceptibility among females to developing cardiometabolic diseases (CMD). Unfortunately, studies investigating the correlation between family planning policies in China and the incidence of CMD remain scarce. Methods: Data from 1,226 females, aged 30 years or older with ≥ 1 live birth, undergoing routine physical examinations between January 2018 and December 2021 were collected, and they were grouped by number of live births 1, 2, and ≥ 3. A binary logistic regression model was employed to examine the association between the number of live births with CMD. Furthermore, the subgroup analysis was performed to elucidate the impact of the implementation of family planning policies with CMD. Results: Women with live births ≥ 3 tended to be older, had higher gravidities, a greater proportion of central obesity, general obesity, hypertension, and dyslipidemia (all P < 0.05). Across the three groups (live birth = 1, =2 and ≥ 3), the odds ratio (OR) with 95% CI for obesity were: 1.00, 3.32 (2.36–4.69), and 5.73 (3.79–8.68); for dyslipidemia were: 1.00, 1.75 (1.29–2.39), and 2.02 (1.38–2.94); and for CMD were: 1.00, 1.91 (1.44–2.54), and 2.15 (1.46–3.15), respectively (all P < 0.05). In addition, based on the different periods of the childbearing policy in China, a subgroup analysis (where age was divided into ≤ 45, 45–65, and ≥ 65 years old) found that each additional live birth increased the prevalence risk of obesity and CMD in the younger generations, while hypertension and dyslipidemia in the elder generation. Conclusions: Higher live births are positively associated with the prevalence of CMD among women in Southwest China. Moreover, giving birth after the implementation of the one-child policy tends to have a higher risk of developing CMD. [ABSTRACT FROM AUTHOR]

Background: The role of dietary fat quality in promotion of cardiovascular diseases is studies before. However, the results are inconsistent. Recently, cholesterol to saturated fatty acid index (CSI) is suggested as a novel indicator of the atherogenicity and thrombogenicity potential of a diet. However, due to limited number of studies, in the current cross-sectional study, we aimed to evaluate the role of CSI in metabolic and inflammatory response among obese individuals. Methods: In the current cross-sectional study 488 obese individuals aged 18–50 years old were involved in volunteer based invitation from outpatient obesity clinics. Subjects underwent anthropometric assays including weight, height, waist circumference (WC) and body composition and their fasting blood sample were obtained for biochemical assessments including blood sugar, serum lipids, hs-CRP and IL-6 concentrations by commercial kits. Physical activity was also assessed by short form of international physical activity questionnaire (IPAQ). Results: According to our results, being at the top tetile of CSI was associated with higher anthropometric indices including weight, height, WC, FFM, and basal metabolic rate (BMR) compared with those at the lowest tertile (P < 0.05). Similarly, those at the highest category of CSI had significantly higher levels of serum glucose and hs-CRP both in crude and adjusted models in ANCOVA and in multinomial logistic regression models (P < 0.05). Conclusion: In the current study, for the first time, we identified the possible triggering role of dietary cholesterol to saturated fat index in increasing serum glucose and hs-CRP levels. due to cross-sectional design of the current study, causal inference is impossible. Further studies will help for better scientific justification. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) and obesity are prevalent metabolic disorders in the Indian population, often linked to lifestyle changes leading to metabolic alterations. Elevated levels of circulating saccharides contribute to various metabolic disturbances, including T2DM and associated complications such as renal and retinal dysfunction. This study aimed to identify individuals at risk of T2DM through lipid profiling in Bhiwadi, Rajasthan. A total of 800 participants were enrolled, and parameters including lipid profiling levels (HDL, Cholesterol) were assessed. Among the participants, 400 males and 400 females exhibited lipid profiles indicative of T2DM risk. These findings underscore the significance of lipid profiling in identifying individuals at risk of T2DM and obesity-related complications. Lifestyle modifications and targeted interventions are crucial to mitigate the growing burden of these metabolic disorders, particularly in regions like Bhiwadi, Rajasthan, India. [ABSTRACT FROM AUTHOR]

Background: The influence of alcohol intake on metabolic dysfunction‐associated fatty liver disease (MAFLD) development and remission remains unclear; thus, we aimed to investigate their longitudinal associations. Methods: This observational cohort study included 6349 patients who underwent more than two health check‐ups over >2 years between April 2013 and March 2021. Generalized estimation equations were used to analyse the longitudinal associations between changes in alcohol intake and MAFLD according to repeated measures at baseline and the most recent stage. Results: The MAFLD development and remission rates were 20.4 and 5.1 and 9.1 and 4.7% in men and women, respectively. Although alcohol consumption was not a significant factor for MAFLD development, consuming 0.1–69.9 g/week (odds ratio [OR]: 0.672, 95% confidence interval [CI]: 0.469–0.964, p <.05) and ≥280 g/week were significant factors for MAFLD development in males (OR: 1.796, 95% CI: 1.009–3.196, p <.05) and females (OR: 16.74, 95% CI: 3.877–72.24, p <.001). Regardless of quantity and frequency, alcohol consumption was not a significant factor for MAFLD remission. Several noninvasive liver fibrosis scores were significantly associated with alcohol intake quantity and frequency in males with MAFLD development and remission (p <.05). The nonalcoholic fatty liver disease fibrosis score differed significantly between males with and without reduced alcohol intake (p <.05) who showed MAFLD remission. Conclusions: Although the influence of alcohol intake on MAFLD development and remission differed, alcohol consumption was not beneficial for MAFLD remission in either sex. Alcohol intake reduction or cessation is recommended to prevent liver fibrosis, even in those who achieve MAFLD remission. [ABSTRACT FROM AUTHOR]

Summary: Human skeletal muscle mitochondria regulate energy expenditure. Research has shown that the functionality of muscle mitochondria is altered in subjects with overweight, as well as in response to nutrient excess and calorie restriction. Two metabolic features of obesity and overweight are (1) incomplete muscular fatty acid oxidation and (2) increased circulating lactate levels. In this study, I propose that these metabolic disturbances may originate from a common source within the muscle mitochondrial electron transport system. Specifically, a reorganization of the supramolecular structure of the electron transport chain could facilitate the maintenance of readily accessible coenzyme Q pools, which are essential for metabolizing lipid substrates. This approach is expected to maintain effective electron transfer, provided that there is sufficient complex III to support the Q‐cycle. Such an adaptation could enhance fatty acid oxidation and prevent mitochondrial overload, thereby reducing lactate production. These insights advance our understanding of the molecular mechanisms underpinning metabolic dysregulation in overweight states. This provides a basis for targeted interventions in the quest for metabolic health. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is associated with obesity and, therefore, it is important to target both overweight and hyperglycaemia. Glucagon plays important roles in glucose, amino acid and fat metabolism and may also regulate appetite and energy expenditure. These physiological properties are currently being exploited therapeutically in several compounds, most often in combination with glucagon‐like peptide‐1 (GLP‐1) agonism in the form of dual agonists. With this combination, increases in hepatic glucose production and hyperglycaemia, which would be counterproductive, are largely avoided. In multiple randomized trials, the co‐agonists have been demonstrated to lead to significant weight loss and, in participants with T2DM, even improved glycated haemoglobin (HbA1c) levels. In addition, significant reductions in hepatic fat content have been observed. Here, we review and discuss the studies so far available. Twenty‐six randomized trials of seven different GLP‐1 receptor (GLP‐1R)/glucagon receptor (GCGR) co‐agonists were identified and reviewed. GLP‐1R/GCGR co‐agonists generally provided significant weight loss, reductions in hepatic fat content, improved lipid profiles, insulin secretion and sensitivity, and in some cases, improved HbA1c levels. A higher incidence of adverse effects was present with GLP‐1R/GCGR co‐agonist treatment than with GLP‐1 agonist monotherapy or placebo. Possible additional risks associated with glucagon agonism are also discussed. A delicate balance between GLP‐1 and glucagon agonism seems to be of particular importance. Further studies exploring the optimal ratio of GLP‐1 and glucagon receptor activation and dosage and titration regimens are needed to ensure a sufficient safety profile while providing clinical benefits. [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations of metabolic score for insulin resistance (METS‐IR) with all‐cause and cardiovascular disease (CVD)‐specific mortality and the potential mediating role of biological ageing. Methods: A cohort of 19 204 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 was recruited for this study. Cox regression models, restricted cubic splines, and Kaplan–Meier survival curves were used to determine the relationships of METS‐IR with all‐cause and CVD‐specific mortality. Mediation analyses were performed to explore the possible intermediary role of biological ageing markers, including phenotypic age (PhenoAge) and biological age (BioAge). Results: During a median follow‐up of 9.17 years, we observed 2818 deaths, of which 875 were CVD‐specific. Multivariable Cox regression showed that the highest METS‐IR level (Q4) was associated with increased all‐cause (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.14–1.67) and CVD mortality (HR 1.52, 95% CI 1.10–2.12) compared with the Q1 level. Restricted cubic splines showed a nonlinear relationship between METS‐IR and all‐cause mortality. Only METS‐IR above the threshold (41.02 μg/L) was positively correlated with all‐cause death. METS‐IR had a linear positive relationship with CVD mortality. In mediation analyses, we found that PhenoAge mediated 51.32% (p < 0.001) and 41.77% (p < 0.001) of the association between METS‐IR and all‐cause and CVD‐specific mortality, respectively. For BioAge, the mediating proportions of PhenoAge were 21.33% (p < 0.001) and 15.88% (p < 0.001), respectively. Conclusions: This study highlights the detrimental effects of insulin resistance, as measured by METS‐IR, on all‐cause and CVD mortality. Moreover, it underscores the role of biological ageing in mediating these associations, emphasizing the need for interventions targeting both insulin resistance and ageing processes to mitigate mortality risks in metabolic disorders. [ABSTRACT FROM AUTHOR]

Obesity has become a major global problem that significantly confers an increased risk of developing life‐threatening complications, including type 2 diabetes mellitus, fatty liver disease and cardiovascular diseases. Protein arginine methyltransferases (PRMTs) are enzymes that catalyse the methylation of target proteins. They are ubiquitous in eukaryotes and regulate transcription, splicing, cell metabolism and RNA biology. As a key, epigenetically modified enzyme, protein arginine methyltransferase 1 (PRMT1) is involved in obesity‐related metabolic processes, such as lipid metabolism, the insulin signalling pathway, energy balance and inflammation, and plays an important role in the pathology of obesity‐related metabolic disorders. This review summarizes recent research on the role of PRMT1 in obesity‐related metabolic disorders. The primary objective was to comprehensively elucidate the functional role and regulatory mechanisms of PRMT1. Moreover, this study attempts to review the pathogenesis of PRMT1‐mediated obesity‐related metabolic disorders, thereby offering pivotal information for further studies and clinical treatment. [ABSTRACT FROM AUTHOR]

Obesity has a pivotal and multifaceted role in pain associated with osteoarthritis (OA), extending beyond the mechanistic influence of BMI. It exerts its effects both directly and indirectly through various modifiable risk factors associated with OA-related pain. Adipose tissue dysfunction is highly involved in OA-related pain through local and systemic inflammation, immune dysfunction, and the production of pro-inflammatory cytokines and adipokines. Adipose tissue dysfunction is intricately connected with metabolic syndrome, which independently exerts specific effects on OA-related pain, distinct from its association with BMI. The interplay among obesity, adipose tissue dysfunction and metabolic syndrome influences OA-related pain through diverse pain mechanisms, including nociceptive pain, peripheral sensitization and central sensitization. These complex interactions contribute to the heightened pain experience observed in individuals with OA and obesity. In addition, pain management strategies are less efficient in individuals with obesity. Importantly, therapeutic interventions targeting obesity and metabolic syndrome hold promise in managing OA-related pain. A deeper understanding of the intricate relationship between obesity, metabolic syndrome and OA-related pain is crucial and could have important implications for improving pain management and developing innovative therapeutic options in OA. In this Review, the authors explore the complex interactions between osteoarthritis-related pain and obesity, adipose tissue dysfunction and metabolic syndrome, and discuss how knowledge of these relationships could help improve pain management and identify new therapeutic options. Key points: Obesity serves as an important risk factor for pain in osteoarthritis (OA) and is associated with all modifiable risk factors related to OA-related pain. Adipose tissue dysfunction has a specific role in OA-related pain independently of BMI. Serum and synovial fluid levels of leptin are closely associated with OA-related pain after adjustment for BMI, whereas the role of adiponectin in OA pain is controversial. Metabolic syndrome is associated with OA-related pain independently of BMI. Obesity modulates nociceptive, neuropathic-like and nociplastic pain through neuromodulators and both peripheral and central sensitization. Therapeutics used in the treatment of obesity and metabolic syndrome could also hold promise for the management of OA-related pain, particularly GLP1R agonists. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity. Methods: This is a prospective case–control study with collection of cerebrospinal fluid (CSF), serum, and clinical data from new‐onset, treatment‐naïve patients with IIH (n = 60). Patients were included consecutively from 2 tertiary headache centers in Denmark, and age, sex, and body mass index (BMI) ‐matched healthy controls (n = 35) were recruited. Clinical data were retrieved at ocular remission (n = 55). Samples were analyzed using non‐targeted mass spectrometry. Results: Serum sphingosine 1‐phosphate (S1P), adenosine, and glutamate were 0.46‐fold (q < 0.0001), 0.25‐fold (q = 0.0048), and 0.44‐fold (q < 0.0001) lower, respectively, in IIH. CSF stearoyl‐lysophosphatidylcholine (LysoPC‐18) and 2‐palmitoyl‐lysophosphatidylcholine (LysoPC‐16) were 0.42 (q = 0.0025) and 0.37 (q < 0.001) ‐fold lower. LysoPC‐18 was higher in patients with moderate–severe versus mild papilledema (p = 0.022). LysoPC‐18 correlated positively with retinal nerve fiber layer thickness (p = 0.0012, r = 0.42) and inversely with mean deviation on automated perimetry (p = 0.01, r = −0.35). Higher baseline serum S1P (p = 0.018) and lower CSF LysoPC‐16 (p = 0.003) were associated with optic nerve atrophy at ocular remission. Pathway analysis suggests dysregulated lipid metabolism and redox disturbances in new‐onset IIH. Interpretation: We identify perturbed metabolism in new‐onset IIH. S1P and LysoPC‐16 demonstrate potential prognostic value due to association with subsequent optic nerve atrophy. This association between specific, differential metabolites and outcome provides substantial evidence for novel biomarkers of clinical significance that should be the focus of further targeted studies. ANN NEUROL 2024;96:595–607 [ABSTRACT FROM AUTHOR]

Background: Glucosamine is a dietary supplement commonly used to support joint health. However, there has been interest in exploring other effects of glucosamine on health outcomes due to its ant‐inflammation effect. Objective: This study compared the risks of major adverse liver outcomes (MALOs) between regular users and non‐users of glucosamine among patients with type 2 diabetes and metabolic dysfunction associated steatotic liver disease (MASLD) using the data from a large prospective cohort study. Methods: Demographic, anthropometric, laboratory and medication prescription information among 18 753 patients with type 2 diabetes and MASLD was obtained from the UK Biobank. MASLD was identified based on hepatic steatosis defined by fatty liver index ≥60 plus the presence of any clues of metabolic dysregulation and cardio‐metabolic risk factors, excluding patients with moderate to severe alcohol consumption. Results: During a mean follow‐up of 11.4 years, 826 incident MALOs events were recorded. Patients not regularly using glucosamine compared with patients using glucosamine showed a significantly higher risk of the composite MALOs (HR 1.36, 95% confidence interval [CI] 1.09–1.69) as well as most individual MALOs except for ascites. The multivariable‐adjusted HRs of MALOs within 3, 5 and 10 years among non‐users of glucosamine compared with regular users were 1.79 (95% CI.69–2.03), 1.88 (95% CI 1.21–2.54) and 1.32 (95% CI 1.05–1.72), respectively. Further subgroup analyses in participants with different baseline characteristics and sensitivity analyses excluding participants who regularly took any other supplements and participants who used self‐reports to diagnose diabetes confirmed the findings. Conclusions: The present study indicated that habitual use of glucosamine was associated with a low risk of individual and composite MALOs among patients with type 2 diabetes and MASLD. [ABSTRACT FROM AUTHOR]

Seaweed polysaccharides (SPs) obtained from seaweeds are a class of functional prebiotics. SPs can regulate glucose and lipid anomalies, affect appetite, reduce inflammation and oxidative stress, and therefore have great potential for managing metabolic syndrome (MetS). SPs are poorly digested by the human gastrointestinal tract but are available to the gut microbiota to produce metabolites and exert a series of positive effects, which may be the mechanism by which SPs render their anti-MetS effects. This article reviews the potential of SPs as prebiotics in the management of MetS-related metabolic disturbances. The structure of SPs and studies related to the process of their degradation by gut bacteria and their therapeutic effects on MetS are highlighted. In summary, this review provides new perspectives on SPs as prebiotics to prevent and treat MetS. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound. Its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after exposure to BPA (10 mg/L via drinking water for 90 days). Four groups were taken in this study – Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress, and antioxidants were also determined. HFD + BPA group rats showed a significant decline in memory function in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule-associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor– kappa B (NF-КB) in the brain. Obesity also caused significant (p < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (p < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases. [ABSTRACT FROM AUTHOR]

There may be an increased risk of metabolic disorders, such as rumen acidosis, in cattle fed high‐concentrate diets, particularly those from Bos taurus indicus genotypes, which have shown to be more sensitive to ruminal acidification. Therefore, this study aimed to estimate (co)variance components and identify genomic regions and pathways associated with ruminal acidosis in feedlot Nellore cattle fed high‐concentrate diets. It was utilized a dataset containing a total of 642 Nellore bulls that were genotyped from seven feedlot nutrition studies. The GGP Indicus 35k panel was used with the single step genome‐wide association study methodology in which the effects of the markers were obtained from the genomic values estimated by the GBLUP model. A bivariate model to estimate genetic correlations between the economically important traits and indicator traits for acidosis was used. The traits evaluated in this study that were nutritionally related to rumen acidosis included average daily gain (ADG), final body weight, time spent eating (TSE), time spent ruminating, rumenitis score (RUM), rumen absorptive surface area (ASA), rumen keratinized layer thickness (KER) and hot carcass weight (HCW). The identified candidate genes were mainly involved in the negative or non‐regulation of the apoptotic process, salivary secretion, and transmembrane transport. The genetic correlation between HCW and ASA was low positive (0.27 ± 0.23), and between ADG and ASA was high moderate (0.58 ± 0.59). A positive genetic correlation between RUM and all performance traits was observed, and TSE correlated negatively with HCW (−0.33 ± 0.21), ASA (−0.75 ± 0.48), and KER (−0.40 ± 0.27). The genetic association between economically important traits and indicator traits for acidosis suggested that Nellore cattle may be more sensitive to acidosis in feedlot systems. [ABSTRACT FROM AUTHOR]

Flavin containing monooxygenase 3 (FMO3) is a member of the flavin monooxygenase family, which can oxidize the precursor Trimethylamine (TMA) provided from food to produce Trimethylamine N-oxide (TMAO). The autosomal recessive inherited disease caused by partial functional loss of Fmo3 gene, which leads to excessive excretion of TMA in body fluids and emits fishy odor, is called Fish Odor Syndrome or Trimethylaminuria. This disease has been documented for 3,000 years ago and was first reported in the case report in 1970. FMO3 mainly exists in the liver and can participate in the TMA-TMAO metabolic balance in intestinal microorganisms, liver, and kidneys, closely related to insulin resistance, diabetes, cholesterol metabolism, and cardiovascular disease. Due to its wide range of catalytic substrates and low susceptibility to metabolite accumulation, its role in drug metabolism, new drug development, and discovery of new drug targets are increasingly valued. This review will summarize the research progress on the metabolic process and localization of FMO3, congenital genetic defects, metabolic diseases, and its related possible mechanisms. [ABSTRACT FROM AUTHOR]

Background: Male androgenetic alopecia (MAA) is a multifactorial disease, with patients presenting at a younger age, which is a risk factor for many metabolic diseases. Aims: To explore the risk factors associated with early‐onset of MAA and its metabolic characteristics. Methods: Forty patients with MAA and 45 healthy controls were collected. The serum levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), total testosterone (TT), uric acid (UA), and 25‐hydroxyvitamin D (25(OH)D) were measured. Meanwhile, lipid metabolites were detected by ultra‐high‐performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Results: 37.50% MAA patients had metabolic syndrome, compared to 17.78% in control group (p < 0.05). The levels of HDL‐C, UA, and 25(OH)D were decreased in patients with MAA compared to healthy controls (p < 0.05). However, there was no significant difference in the level of TT between the two groups. Additionally, there were no significant differences in the levels of HDL‐C, UA, 25(OH)D, and TT among different grades of hair loss (p > 0.05). The lipid profile of early‐onset MAA differed significantly from healthy controls. In early‐onset MAA, the levels of ceramide (Cer) and sphingomyelin (SM) were significantly lower. Cer(d38:5) and TG(15:0/18:1/18:1) may be the biomarkers. Conclusion: Low HDL‐C, UA, and 25(OH)D may be the independent risk factors for early‐onset MAA. Abnormal lipid metabolism was observed in early‐onset MAA, wherein Cer and SM may serve as protective factors. [ABSTRACT FROM AUTHOR]

β‐arrestin2, a member of the arrestin family, mediates the desensitization and internalization of most G protein‐coupled receptors (GPCRs) and functions as a scaffold protein in signalling pathways. Previous studies have demonstrated that β‐arrestin2 expression is dysregulated in malignant tumours, fibrotic diseases, cardiovascular diseases and metabolic diseases, suggesting its pathological roles. Transcription and post‐transcriptional modifications can affect the expression of β‐arrestin2. Furthermore, post‐translational modifications, such as phosphorylation, ubiquitination, SUMOylation and S‐nitrosylation affect the cellular localization of β‐arrestin2 and its interaction with downstream signalling molecules, which further regulate the activity of β‐arrestin2. This review summarizes the structure and function of β‐arrestin2 and reveals the mechanisms involved in the regulation of β‐arrestin2 at multiple levels. Additionally, recent studies on the role of β‐arrestin2 in some major diseases and its therapeutic prospects have been discussed to provide a reference for the development of drugs targeting β‐arrestin2. [ABSTRACT FROM AUTHOR]

Obesity compromises metabolic flexibility and increases specific immune responses. Fasting forces metabolic flexibility and alters glucose, fatty acids, glycerol, and amino acids to maintain blood glucose and energy balance. Intermittent fasting (IF) lowers inflammation and opposes metabolic dysfunction during obesity. IF can improve glucose metabolism independent of changes in obesity. Gut microbiota composition altered by IF triggers changes in immunity and metabolism. Intermittent fasting (IF) modifies cell- and tissue-specific immunometabolic responses that dictate metabolic flexibility and inflammation during obesity and type 2 diabetes (T2D). Fasting forces periods of metabolic flexibility and necessitates increased use of different substrates. IF can lower metabolic inflammation and improve glucose metabolism without lowering obesity and can influence time-dependent, compartmentalized changes in immunity. Liver, adipose tissue, skeletal muscle, and immune cells communicate to relay metabolic and immune signals during fasting. Here we review the connections between metabolic and immune cells to explain the divergent effects of IF compared with classic caloric restriction (CR) strategies. We also explore how the immunometabolism of metabolic diseases dictates certain IF outcomes, where the gut microbiota triggers changes in immunity and metabolism during fasting. [ABSTRACT FROM AUTHOR]

Given its nonnegligible role in metabolic homeostasis, adipose tissue has been the target for treating metabolic disorders such as obesity, diabetes and cardiovascular diseases. Besides its lipolytic function, adipose thermogenesis has gained increased interest due to the irreplaceable contribution to dissipating energy to restore equilibrium, and its therapeutic effects have been testified in various animal models. In this review, we will brief about the canonical cold-stimulated adipose thermogenic mechanisms, elucidate on the exercise- and intermittent fasting-induced adipose thermogenic mechanisms, with a focus on the similarities and disparities among these signaling pathways, in an effort to uncover the overlapped and specific targets that may yield potent therapeutic efficacy synergistically in improving metabolic health. • Adipose thermogenic mechanisms induced by cold exposure, exercise and intermittent fasting share similar signaling pathways. • Certain adipose thermogenic mechanisms induced by exercise are distinctive. • Adipose thermogenesis has been applied in treatment for various diseases. • Similarities and disparities in adipose thermogenic mechanisms shed new light on treating diseases. [ABSTRACT FROM AUTHOR]

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The objective of this study was to analyse an individual whose remains are characterised by early deciduous tooth loss and multi-focal lesions on the post-cranial skeleton. Skeletal remains of an immature individual buried between 1770 and 1849 in London. The remains were examined by visual macroscopic inspection, supplemented by radiographic examination of the mandible and maxillae. A differential diagnosis with possible conditions, frequent in this archaeological context, was conducted. A comprehensive examination of dental lesions was performed to investigate the aetiologies of deciduous tooth loss. The individual exhibited a mosaic of skeletal and dental pathological changes, including premature loss of deciduous dentition, premature eruption of permanent teeth generalised bone loss in both the mandible and maxilla; osteomyelitis of the left radius; osteolytic lesion on the body of the second lumbar vertebra, and marked expansions of the rib shafts due to sub-periosteal new bone formation. A differential diagnosis considered indicates that the pathological changes of the individual were most likely associated with a comorbidity involving hypophosphatasia and tuberculosis. We present in this study several oral signs that could alert paleopathologists and bioarcheologists to systematically consider the potential of a condition that is rarely encountered in archaeological contexts. Due to poor preservation, this study was confined to the analysis of a partial maxilla and mandible, a left radius shaft and the axial skeleton (rib heads and vertebrae) of the individual. Further radiographic, histological and genetic analyses would confirm the diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Sleeve gastrectomy (SG) is the most performed metabolic and bariatric surgery (MBS). However, with the increase of SG in different regions, recurrent weight gain after SG is challenging for bariatric surgeons. We introduce a modified operation with a long, narrow pouch in RYGB (LN-RYGB) for weight regain after SG which enhanced the restrictive function in RYGB. Methods and Results: The LN-RYGB has a longer and narrow gastric pouch for 10 cm. The length of small Roux and biliopancreatic are the same as RYGB. As a revisional surgery, the post-1 year excess weight loss percentage (%EWL) was 63.1% and total weight loss percentage (%TWL) was 29.1% in 5 cases. Conclusion: LN-RYGB is an optional treatment for recurrent weight gain after SG; a randomized control trial is needed to verify the long-term effect of LN-RYGB. [ABSTRACT FROM AUTHOR]

Context Surrogate measures of childhood and adolescent obesity have impaired the understanding of the relationship of body composition with insulin resistance in the young population. Objective We aim to examine the longitudinal associations of directly measured total fat mass, trunk fat mass, and lean mass with the risk of hyperglycemia, hyperinsulinemia, and insulin resistance from ages 15 to 24 years, the mediation path through which lipids and inflammation influence insulin resistance, and whether increased fat mass temporally precede insulin resistance. Methods We studied 3160 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, who had complete dual-energy x-ray absorptiometry measure and fasting blood samples at age 15 years and repeated measures at ages 17- and 24-years clinic visit. Fasting glucose greater than 6.1 mmol/L, insulin greater than 11.78 mU/L, and homeostatic model assessment for insulin resistance (HOMA-IR) greater than or equal to the 75th percentile were categorized as hyperglycemia, hyperinsulinemia, and high insulin resistance, respectively. Longitudinal associations were examined with generalized logit-mixed-effect models, while mediation and temporal path analyses were examined using structural equation models, adjusting for cardiometabolic and lifestyle factors. Results Among 3160 participants (51% female), fat mass and lean mass increased linearly both in males and females, while glucose, insulin, and HOMA-IR had a U-shaped course from age 15 through 24 years. After full adjustment, each 1-kg cumulative increase in total fat mass (odds ratio 1.12 [95% CI, 1.11-1.13]) and trunk fat mass (1.21 [1.19-1.23]) from ages 15 through 24 years were associated with a progressively worsening risk of high insulin resistance as well as hyperglycemia and hyperinsulinemia. The association of increased total fat mass with increased insulin resistance was partly mediated by triglycerides (9% mediation). In the temporal path analysis, higher total fat mass at age 15 years was associated with higher insulin resistance at age 17 years, but not vice versa. Higher total fat mass at age 17 years was bidirectionally associated with higher insulin resistance at 24 years. Conclusion Mid-adolescence may be an optimal time for interrupting the worsening fat mass–insulin resistance pathologic cycle and attenuating the risk of progressively worsening metabolic dysfunction before young adulthood. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a heavy metal that acts as endocrine disrupting chemical (EDC). Few studies have investigated the effects of Cd exposure on metabolic dysfunctions, such as type 1 and 2 diabetes mellitus (T1DM and T2DM). Thus, we assessed whether subacute Cd exposure at occupational levels causes abnormalities in white adipose tissue (WAT), liver, pancreas, and skeletal muscle. We administered cadmium chloride (CdCl2) (100 ppm in drinking water for 30 days) to female rats and evaluated Cd levels in serum and metabolic organs, morphophysiology, inflammation, oxidative stress, fibrosis, and gene expression. High Cd levels were found in serum, WAT, liver, pancreas, and skeletal muscle. Cd‐exposed rats showed low adiposity, dyslipidemia, insulin resistance, systemic inflammation, and oxidative stress compared to controls. Cd exposure reduced adipocyte size, hyperleptinemia, increased cholesterol levels, inflammation, apoptosis and fibrosis in WAT. Cd‐exposed rats had increased liver cholesterol levels, insulin receptor beta (IRβ) and peroxisome proliferator‐activated receptor‐gamma coactivator‐1alpha (PGC1α) expression, karyomegaly, inflammation, and fibrosis. Cd exposure reduced insulin levels and pancreatic islet size and increased inflammation and fibrosis. Cd exposure reduced skeletal muscle fiber diameter and increased IR expression and inflammation. Finally, strong positive correlations were observed between serum, tissue Cd levels, abnormal morphology, tissue inflammation and fibrosis. Thus, these data suggest that subacute Cd exposure impairs WAT, liver, pancreas and skeletal muscle function, leading to T1DM and T2DM features and other complications in female rats. [ABSTRACT FROM AUTHOR]

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Introduction and purpose : Type 2 diabetes is currently a serious problem worldwide. Each year, the number of individuals with carbohydrate metabolism disorders is increasing. This is due to an unhealthy lifestyle, lack of physical activity, and a diet rich in highly processed foods. Currently, the treatment of type 2 diabetes is based on the use of oral antidiabetic medications, with the first choice often being a derivative of biguanides, such as metformin. Berberine has been used in China for many years as a hypoglycemic agent, and its efficacy is compared to metformin preparations. This paper focuses on the benefits of using berberine in patients with prediabetes or type 2 diabetes and compares the effects of berberine preparations to classical medications used in diabetes treatment. Material and methods : The literaue was reviewed in PubMed and Google Scholar scientific database in 2013-2023 using the following keywords : berberine, diabetes mellitus type 2, hyperlipidemia, hyperglicemia. Conclusions : The studies included in this manuscript have shown that berberine is a promising agent for adjunctive treatment in type 2 diabetes. It exhibits a range of positive effects such as lowering blood glucose levels, improving lipid profile, with no serious adverse effects reported. However, further research is needed to confirm these findings and develop an effective treatment plan. [ABSTRACT FROM AUTHOR]

Au@Pt nanozyme, a bimetallic core–shell structure Au and Pt nanoparticle, has attracted significant attention due to its excellent catalytic activity and stability. Here, we propose that Au@Pt improves glucose tolerance and reduces TG after four weeks administration. The transcriptomic analysis of mouse liver tissues treated with Au@Pt nanozyme showed changes in genes related to glucose and lipid metabolism signaling pathways, including glycolysis/gluconeogenesis, pyruvate metabolism, PPAR signaling, and insulin signaling. Moreover, analysis of fecal samples from mice treated with Au@Pt nanozyme showed significant changes in the abundance of beneficial gut microbiota such as Dubosiella, Parvibacter, Enterorhabdus, Monoglobus, Lachnospiraceae_UCG-008, Lachnospiraceae_UCG-006, Lachnospiraceae_UCG-001, and Christensenellaceae_R-7_group. Combined multi-omics correlation analyses revealed that the modulation of glucose and lipid metabolism by Au@Pt was strongly correlated with changes in hepatic gene expression profiles as well as changes in gut microbial profiles. Overall, our integrated multi-omics analysis demonstrated that Au@Pt nanozyme could modulate glucose and lipid metabolism by regulating the expression of key genes in the liver and altering the composition of gut microbiota, providing new insights into the potential applications of Au@Pt nanozyme in the treatment of metabolic disorder. [ABSTRACT FROM AUTHOR]

• Silent Alzheimer's disease impacts hypothalamus and hippocampus transcriptome. • AppNL-G-F mice show change in several biomarkers prior to cognitive decline. • Leptin levels are decreased during silent phase of Alzheimer's in AppNL-G-F mice. • Inflammatory mediators are increased during silent phase in AppNL-G-F mice. • Transcriptome changes during the silent phase persists during active disease phase. The progression of Alzheimer's disease (AD) has a silent phase that predates characteristic cognitive decline and eventually leads to active cognitive deficits. Metabolism, diet, and obesity have been correlated to the development of AD but is poorly understood. The hypothalamus is a brain region that exerts homeostatic control on food intake and metabolism and has been noted to be impacted during the active phase of Alzheimer's disease. This study, in using an amyloid overexpression AppNL-G-F mouse model under normal metabolic conditions, examines blood markers in young and old male AppNL-G-F mice (n = 5) that corresponds to the silent and active phases of AD, and bulk gene expression changes in the hypothalamus and the hippocampus. The results show a large panel of inflammatory mediators, leptin, and other proteins that may be involved in weakening the blood brain barrier, to be increased in the young AppNL-G-F mice but not in the old AppNL-G-F mice. There were also several differentially expressed genes in both the hypothalamus and the hippocampus in the young AppNL-G-F mice prior to amyloid plaque formation and cognitive decline that persisted in the old AppNL-G-F mice, including GABRa2 receptor, Wdfy1, and several pseudogenes with unknown function. These results suggests that a larger panel of inflammatory mediators may be used as blood markers to detect silent AD, and that a change in leptin and gene expression in the hypothalamus exist prior to cognitive effects, suggesting a coupling of metabolism with amyloid plaque induced cognitive decline. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) represents a heterogeneous and multifactorial metabolic disorder, leading to diverse economic challenges and health complications, significantly affecting individuals’ lives. Type 2 diabetes (T2DM) stands as the predominant form of diabetes, with its onset influenced by a range of genetic and environmental factors. Currently, conventional diabetic medications are employed in clinical practice, but they may entail certain side effects. Fortunately, diverse natural polysaccharides extracted from plants exhibit antidiabetic properties, which have been demonstrated to effectively mitigate hyperglycemia, reverse insulin resistance, and forestall complications associated with diabetes. Consequently, exploring the utilization of these polysaccharides as adjuncts to conventional therapies has emerged as a novel research direction in recent years. Thus, this review centers on the extraction, purification, and characterization of plant polysaccharides, providing an overview of the advancements in the antidiabetic effects and mechanisms of natural polysaccharides. This perspective offers fresh insights to explore potential research domains and enhances understanding for the development of diabetic drugs derived from polysaccharides. [ABSTRACT FROM AUTHOR]

Background: Glucose metabolic disorder is associated with the risk of heart failure (HF). Adiposity is a comorbidity that is inextricably linked with abnormal glucose metabolism in older individuals. However, the effect of adiposity on the association between glucose metabolic disorder and HF risk, and the underlying mechanism remain unclear. Methods: A total of 13,251 participants aged ≥ 60 years from a cohort study were categorized into euglycemia, prediabetes, uncontrolled diabetes, and well-controlled diabetes. Adiposity was assessed using body mass index (BMI), waist-to-hip ratio (WHR), and visceral fat area (VFA). Adiposity-associated metabolic activities were evaluated using adiponectin-to-leptin ratio (ALR), homeostatic model assessment of insulin resistance (HOMA-IR), and triglyceride-glucose index (TyG). The first occurrence of HF served as the outcome during the follow-up period. Results: A total of 1,138 participants developed HF over the course of an average follow-up period of 10.9 years. The rate of incident HF occurrence was higher in prediabetes, uncontrolled diabetes, and well-controlled diabetes participants compared to that in euglycemia participants. However, the high rates were significantly attenuated by BMI, VFA, and WHR. For WHR in particular, the hazard ratio for incident HF was 1.18 (95% confidence interval (CI): 1.03, 1.35, Padj.=0.017) in prediabetes, 1.59 (95% CI: 1.34, 1.90, Padj.<0.001) in uncontrolled diabetes, and 1.10 (95% CI: 0.85, 1.43, Padj.=0.466) in well-controlled diabetes. The population attributable risk percentage for central obesity classified by WHR for incident HF was 30.3% in euglycemia, 50.0% in prediabetes, 48.5% in uncontrolled diabetes, and 54.4% in well-controlled diabetes. Adiposity measures, especially WHR, showed a significant interaction with glucose metabolic disorder in incident HF (all Padj.<0.001). ALR was negatively associated and HOMA-IR and TyG were positively associated with BMI, WHR, VFA, and incident HF (all Padj.<0.05). ALR, HOMA-IR, and TyG mediated the associations for BMI, WHR and VFA with incident HF (all Padj.<0.05). Conclusions: Adiposity attenuated the association of glucose metabolic disorder with incident HF. The results also showed that WHR may be an appropriate indicator for evaluating adiposity in older individuals. Adiposity-associated metabolic activities may have a bridging role in the process of adiposity attenuating the association between glucose metabolic disorder and incident HF. Trial registration: retrospectively registered number: ChiCTR-EOC-17,013,598. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity. Methods: The study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis. Results: Children with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload. Conclusions: Altogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR). Methods: Data of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain. Results: Our investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values. Conclusions: This study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD's adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD. [ABSTRACT FROM AUTHOR]

Background: Follistatin-like protein 1 (FSTL1) has been identified as a secreted glycoprotein that plays an important role in obesity. However, its role in children with metabolic-associated fatty liver disease (MAFLD) has not been investigated. This study aimed at characterizing the relationship between serum FSTL1 concentration and MAFLD in children with obesity. Methods: A total of 121 subjects were recruited from the Second Affiliated Hospital of Xi'an Jiaotong University, including 45 obese children with MAFLD, 31 obese children without MAFLD, and 45 healthy controls. Anthropometric parameters, biochemical data were measured and circulating FSTL1 levels were detected by ELISA. Results: The levels of FSTL1 in obese children with MAFLD were higher than that in obese children without MAFLD: 1.31 (0.35–2.29) ng/mL vs. 0.55 (0.36–1.38) ng/mL. Correlation analysis illustrated that FSTL1 was associated with nonesterified free fatty acid and leptin (r = 0.278, P < 0.05 and r = 0.572, P < 0.05, respectively). Binary logistic regression suggested that increased FSTL1 was a risk factor for MAFLD in children (OR = 1.105, 95% CI: 1.066–1.269, P < 0.05). Conclusions: Serum FSTL1 concentrations increase in obese children with MAFLD and may have the potential to be a risk factor for MAFLD in children with obesity. [ABSTRACT FROM AUTHOR]

Parasites and obesity are health problems worldwide. Rabbits are production animals yielding one of the healthiest meats, also taking advantage of skin, hair, limbs and excreta. It is among the most frequent pets in some countries and widely used as animal model in research. Psoroptes cuniculi is a mite of high transmission rate, affecting welfare and production and obesity causes multiple metabolic, endocrine and immunological disorders, being an emerging problem in domestic animals. Obesity and acarosis are prolonged stressors, modifying the activity of the hypothalamic-pituitary-adrenal axis that can induce metabolic and behavioral disorders. Alterations caused by comorbidities could be similar to or different from those induced by each morbidity separately. We analyzed the influence of obesity on the infection degree with P. cuniculi and on behavior and production. Rabbit does induced to obesity were infected and mated; behaviors in the open field test, obesity estimation indices and productive parameters at delivery and weaning were analyzed. The acarosis induced a decrease in feed intake and a decrease in body weight, a decrease in locomotor, exploratory and chinning behaviors in normal weight and obese does. The infection induced 23% mortality at birth, obesity 45% and comorbidity 74%, while in normal weight rabbits a 6.5% was observed. Weight gain from birth to weaning was lower in the comorbid group, reaching a litter weight of 4.5±0.13 kg in healthy normal weight does and 2.6±0.67 kg in comorbid does. The disturbances induced by the comorbidity were magnified in both behavioral and productive parameters. [ABSTRACT FROM AUTHOR]

While it is generally known that metabolic disorders and circadian dysfunction are intertwined, how the two systems affect each other is not well understood, nor are the genetic factors that might exacerbate this pathological interaction. Blood chemistry is profoundly changed in metabolic disorders, and we have previously shown that serum factors change cellular clock properties. To investigate if circulating factors altered in metabolic disorders have circadian modifying effects, and whether these effects are of genetic origin, we measured circadian rhythms in U2OS cell in the presence of serum collected from diabetic, obese or control subjects. We observed that circadian period lengthening in U2OS cells was associated with serum chemistry that is characteristic of insulin resistance. Characterizing the genetic variants that altered circadian period length by genome‐wide association analysis, we found that one of the top variants mapped to the E3 ubiquitin ligase MARCH1 involved in insulin sensitivity. Confirming our data, the serum circadian modifying variants were also enriched in type 2 diabetes and chronotype variants identified in the UK Biobank cohort. Finally, to identify serum factors that might be involved in period lengthening, we performed detailed metabolomics and found that the circadian modifying variants are particularly associated with branched chain amino acids, whose levels are known to correlate with diabetes and insulin resistance. Overall, our multi‐omics data showed comprehensively that systemic factors serve as a path through which metabolic disorders influence circadian system, and these can be examined in human populations directly by simple cellular assays in common cultured cells. [ABSTRACT FROM AUTHOR]

BACKGROUND METHODS RESULTS CONCLUSION Obesity is a metabolic disease that affects many individuals around the world, related to imbalance between energy consumption and expenditure, which can lead to comorbidities. A healthy diet can significantly contribute to the prevention or treatment of this condition. Jabuticaba is an emerging fruit presenting a wide range of bioactive compounds and is being extensively studied due to its effects on lipid metabolism. The aim of this study was to evaluate the jabuticaba extract in the anxious‐like behavior and in the lipid and oxidative metabolism in the context of obesity.Forty male Wistar rats divided into five groups were used. The animals received a standard diet and/or a hypercaloric diet and after 60 days of induction, interventions were carried out with jabuticaba extract (5% and 10%) via gavage for 30 days.It can be observed that the jabuticaba extract was able to reverse the anxious behavior observed in obese animals and modulate parameters of lipid and oxidative metabolism. We observed a reduction in cholesterol and triglyceride levels compared to obese animals. Furthermore, we observed an improvement in oxidative parameters, with a reduction in protein carbonylation in the liver and modulation of antioxidant enzymes such as superoxide dismutase and catalase. Contrary to expectations, we did not observe changes in leptin, adiponectin and tumor necrosis factor alpha (TNF‐α) levels.Our work demonstrates that jabuticaba extract can improve metabolic, oxidative and behavioral changes in animals with obesity. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Introduction: We previously documented the beneficial effects of rice bran oil (RBO) on cardiac function and atherogenic cardiometabolic factors in men with coronary artery disease. Therefore, the existing evidence in this area aims to be expanded by investigating the impact of adding RBO to a daily standard diet on emerging insulin resistance surrogate markers, lipid peroxidation, antioxidant status, and metabolic disturbances in individuals with metabolic syndrome (MetSyn) through an open-label controlled trial. Methods: A total of 50 overweight/obese adults (mean body mass index (BMI) = 31.08 kg/m2) with at least 3 MetSyn components were randomly allocated to either the control group, which received a standard diet plan, or the intervention group, which was supplemented with 30 g/d RBO for 8 weeks. BMI, MetSyn components, metabolic score for insulin resistance (METS-IR), triglyceride‒glucose‒BMI (TyG‒BMI), malondialdehyde (MDA), total antioxidant capacity (TAC), and plasma polyphenol levels were measured before and after this open-label trial. Results: Analysis of covariance (ANCOVA) adjusted for baseline values revealed that, compared with patients who received only a standard diet, those who were supplemented with 30 g/d RBO presented significantly lower total cholesterol (P value = 0.005; effect size (ES):-0.92), LDL-cholesterol (P value = 0.048; ES:-0.62), fasting blood glucose (P value = 0.014; ES:-0.77), MDA (P value = 0.002; ES: -1.01), METS-IR (P value < 0.001; ES: -1.24), and TyG-BMI (P value = 0.007; ES:-0.85) after 8 weeks. Additionally, RBO consumption resulted in significantly higher levels of HDL-C (P value = 0.004; ES:0.94) and TAC (P value < 0.0001; ES:2.05). However, no significant changes were noted in BMI, waist circumference, serum triglycerides, plasma polyphenols, or blood pressure. Conclusion: Although the current findings suggest that the hypocholesterolemic, antihyperglycemic, and antioxidative effects of 30 g/d RBO seem to be promising for MetSyn patients, they should be considered preliminary. Therefore, further well-designed clinical trials with larger sample sizes and longer durations are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of high-risk optic disc (HROD) on central retinal vein occlusion (CRVO) in patients with metabolic disorder(s). Design: Retrospective case-control study. Methods: A case-control study involving CRVO patients with metabolic disorder(s) was performed. PART I. All eligible patients with CRVO were included in CRVO group, and a similar number of patients with metabolic disorder(s) without CRVO were matched by sex, age and blood glucose level in the non-CRVO group. Various parameters were compared between groups. The impact of risk factors associated with CRVO was presented as odds ratios (ORs) and 95% confidence interval (95% CI). PART II. All eyes with CRVO that underwent intravitreal treatment (IVT) with a follow-up duration of ≥1 year were divided into non-HROD and HROD groups, and the differences between the two groups were compared. Results: In PART I, a total of 45 and 63 eyes were enrolled in the CRVO and non-CRVO groups, respectively, with a significant statistical difference in HROD (51.16% vs 26.98%, p = 0.010) between them. In further multivariate regression analysis, HROD was the independent risk factor for CRVO (OR = 5.036, 95% CI 1.847-13.729, p = 0.002). In PART II, demographic, follow-up information, treatment, and prognosis showed no significant statistical difference between the two groups (all p > 0.05).* Conclusion: HROD was likely to be an independent risk factor for CRVO occurrence in patients with metabolic disorder(s), but it did not affect the treatment and prognosis of CRVO eyes with HROD. [ABSTRACT FROM AUTHOR]

Introduction: Obesity, a global epidemic, is caused by an imbalance between energy intake and expenditure. The induction of white adipose browning to increase heat production has emerged as a potential effective strategy to address obesity. Ling-gui-zhu-gan (LGZG), a traditional Chinese medicine formula, has been proved to achieve promising results to combat obesity and related metabolic diseases, yet the mechanisms remain largely unexplored. This study aimed to elucidate the anti-obesity properties and the mechanisms of LGZG by investigating its browning effect on 3T3-L1 adipocytes. Methods: LGZG-containing serum obtained by oral administration of LGZG to animals was added to 3T3-L1 adipocytes to simulate in vivo conditions. Results: The results showed that 49 compounds were identified in LGZGcontaining serum by UHPLC-Q-Orbitrap HRMS, including compounds such as atractylenolides and polyporenic acid C, etc. LGZG-containing serum alleviated the lipid accumulation and decreased both intracellular and extracellular triglyceride contents in a dose-dependent manner. This reduction is accompanied by enhanced mitochondrial respiratory and heat production function. Mechanistically, LGZG-containing serum led to a decrease in miR-27b expression and an increase in the mRNA and protein levels of browningrelated markers, including UCP1, PRDM16, PGC-1α, PPARγ, CTBP1, and CTBP2. Further investigation using miR-27b mimic transfection confirmed that miR-27b/PRDM16 pathway might be a potential mechanism by which LGZG-containing serum promotes browning of 3T3-L1 adipocytes. Discussion: These results underscore the therapeutic potential of LGZG in addressing obesity and its associated metabolic disorders through the promotion of adipose browning. [ABSTRACT FROM AUTHOR]

Background: Meningioma is the most common primary brain tumor, with a clear preponderance in women. Obesity is considered a risk factor for the development of meningioma. Obesity is also the clinical hallmark of metabolic syndrome, characterized by glucose intolerance, dyslipidemia, and hypertension. Lifestyle and metabolic factors directly impact overweight and obesity and are therefore potential risk factors for meningioma development. The aim of this study is to assess lifestyle and metabolic factors for meningioma risk in women. Methods: The Cohort of Norway (CONOR) is a nationwide health survey, conducted between 1994 and 2003, including anthropometric measures, blood tests, and health questionnaires. Linkage to the National Cancer Registry enabled the identification of intracranial meningioma during follow-up until December 2018. Results: A total of 81,652 women were followed for a combined total of 1.5 million years, and 238 intracranial meningiomas were identified. Increasing levels of physical activity (HR 0.81; 95% CI 0.68-0.96; p trend <0.02) and parity (HR 0.83; 95% CI 0.71-0.97; p trend <0.03) were negatively associated with meningioma risk. Diabetes mellitus or glucose intolerance increased the risk for meningioma (HR 2.54; 95% CI 1.60-4.05). Overweight and obesity were not associated with meningioma risk, nor was metabolic syndrome. However, participants without metabolic dysfunction had a reduced meningioma risk, while participants with all five metabolic factors present had a 4-fold risk increase for meningioma (HR 4.28; 95% CI 1.34-13.68). Conclusion: Lifestyle factors seem to significantly influence meningioma risk. However, disentangling the complex associations and interactions between factors for meningioma risk will be a challenging task for future studies. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions To assess the disease burden of familial partial lipodystrophy (FPLD) caused by LMNA (FPLD2) and PPARG (FPLD3) variants to augment the knowledge of these rare disorders characterized by selective fat loss and metabolic complications.An observational longitudinal study, including 157 patients (FPLD2: 139 patients, mean age 46 ± 17 years, 70% women; FPLD3: 18 patients, mean age: 44 ± 17 years, 78% women) from 66 independent families in two countries (83 from Turkey and 74 from Spain), was conducted.Patients were diagnosed at a mean age of 39 ± 19 years, 20 ± 16 years after the first clinical signs appeared. Men reported symptoms later than women. Symptom onset was earlier in FPLD2. Fat loss was less prominent in FPLD3. In total, 92 subjects (59%) had diabetes (age at diagnosis: 34 ± 1 years). Retinopathy was more commonly detected in FPLD3 (P < .05). Severe hypertriglyceridaemia was more frequent among patients with FPLD3 (44% vs. 17%, P = .01). Hepatic steatosis was detected in 100 subjects (66%) (age at diagnosis: 36 ± 2 years). Coronary artery disease developed in 26 patients (17%) and 17 (11%) suffered from a myocardial infarction. Turkish patients had a lower body mass index, a higher prevalence of hepatic steatosis, greater triglyceride levels and a tendency towards a higher prevalence of coronary artery disease. A total of 17 patients died, with a mean time to death of 75 ± 3 years, which was shorter in the Turkish cohort (68 ± 2 vs. 83 ± 4 years, P = .01). Cardiovascular events were a major cause of death.Our analysis highlights severe organ complications in patients with FPLD, showing differences between genotypes and Mediterranean countries. FPLD3 presents a milder phenotype than FPLD2, but with comparable or even greater severity of metabolic disturbances. [ABSTRACT FROM AUTHOR]

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle‐aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age‐related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3‐adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18‐month‐old) C57BL/6JN mice. Sustained β3‐AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a favorable adipokine profile. At the cellular level, CL treatment increased uncoupling protein 1 (UCP1)‐dependent thermogenesis in brown adipose tissue (BAT). However, in white adipose tissue (WAT) depots, CL treatment increased glycerol and lipid de novo lipogenesis (DNL) and turnover suggesting the activation of the futile substrate cycle of lipolysis and reesterification in a UCP1‐independent manner. Increased lipid turnover was also associated with the simultaneous upregulation of proteins involved in glycerol metabolism, fatty acid oxidation, and reesterification in WAT. Further, a dose‐dependent impact of CL treatment on inflammation was observed, particularly in subcutaneous WAT, suggesting a potential mismatch between fatty acid supply and oxidation. These findings indicate that chronic β3‐AR stimulation activates distinct cellular mechanisms that increase energy expenditure in BAT and WAT to improve systemic metabolism in aged mice. Considering that people lose BAT with aging, activation of futile lipid cycling in WAT presents a novel strategy for improving age‐related metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Importance Objective Data Sources and Study Selection Results Conclusions and Relevance The recent change in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction‐associated fatty liver disease (MAFLD) and metabolic dysfunction‐associated steatotic liver disease (MASLD) highlights the link between hepatic steatosis and metabolic dysfunction, taking out the stigmata of alcohol.We compared the effects of NAFLD and MAFLD definitions on the risk of overall and cardiovascular (CV) mortality, liver‐related events (LRE), nonfatal CV events (CVE), chronic kidney disease (CKD), and extra‐hepatic cancers (EHC).We systematically searched four large electronic databases for cohort studies (published through August 2023) that simultaneously used NAFLD and MAFLD definitions for examining the risk of mortality and adverse CV, renal, or oncological outcomes associated with both definitions. In total, 21 eligible cohort studies were identified. Meta‐analysis was performed using random‐effects modelling.Compared with those with NAFLD, individuals with MAFLD had significantly higher rates of overall mortality (random‐effect OR 1.12, 95% CI 1.04–1.21, p = .004) and CV mortality (random‐effect OR 1.15, 95% CI 1.04–1.26, p = .004), and a marginal trend towards higher rates of developing CKD (random‐effect OR 1.06, 95% CI 1.00–1.12, p = .058) and EHC events (random‐effect OR 1.11, 95% CI 1.00–1.23, p = .052). We found no significant differences in the risk LREs and nonfatal CVE between MAFLD and NAFLD. Meta‐regression analyses identified male sex and metabolic comorbidities as the strongest risk factors related to the risk of adverse clinical outcomes in MAFLD compared to NAFLD.Individuals with MAFLD have higher rates of overall and CV mortality and higher rates of developing CKD and EHC events than those with NAFLD, possibly due to the dysmetabolic risk profile related to MAFLD. [ABSTRACT FROM AUTHOR]