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Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity 1,2 . However, maintaining weight loss is a considerable challenge, especially as the body seems to retain an obesogenic memory that defends against body weight changes 3,4 . Overcoming this barrier for long-term treatment success is difficult because the molecular mechanisms underpinning this phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show that both human and mouse adipose tissues retain cellular transcriptional changes after appreciable weight loss. Furthermore, we find persistent obesity-induced alterations in the epigenome of mouse adipocytes that negatively affect their function and response to metabolic stimuli. Mice carrying this obesogenic memory show accelerated rebound weight gain, and the epigenetic memory can explain future transcriptional deregulation in adipocytes in response to further high-fat diet feeding. In summary, our findings indicate the existence of an obesogenic memory, largely on the basis of stable epigenetic changes, in mouse adipocytes and probably other cell types. These changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the problematic 'yo-yo' effect often seen with dieting. Targeting these changes in the future could improve long-term weight management and health outcomes., Competing Interests: Competing interests: M.B. received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer-Ingelhiem, Lilly, Novo Nordisk and Sanofi. M.R. received honoraria as a consultant and speaker from AstraZeneca, Boehringer-Ingelheim, Lilly, Novo Nordisk and Sanofi. The other authors declare no competing interests., (© 2024. The Author(s).)

Background: obesity affects many patients with inflammatory bowel disease (IBD). Glucagon-like peptide (GLP)-1 agonists are a promising therapy for obese patients. However, there is a lack of evidence of the use of these drugs in IBD patients. This study investigated the effectiveness and safety of GLP-1 agonists in a cohort of obese patients with IBD., Methods: a retrospective series of cases of consecutive IBD patients who received GLP-1 agonists indicated to treat obesity between 2019 and 2021 was analyzed. The GLP-1 agonists included were semaglutide 1.0 mg or liraglutide 3.0 mg. The coprimary endpoints were the percentage of change in body weight from baseline to six months and a weight reduction of 5 % or more at six months. In addition, the safety profile of GLP-1 agonist therapy and its impact on the IBD course were reviewed., Results: sixteen obese patients with IBD (nine with Crohn's disease [CD] and seven with ulcerative colitis [UC]) were included in the study. The median body mass index at baseline was 35 (32-37). The percentage of change in body weight was -6.2 % (-3.4-[-8.5]) at six months, and a 5 % or more weight reduction was achieved in 58.3 % (7/12) of patients at six months. The most common side effect was nausea (13.3 %), and one patient withdrew due to diarrhea. IBD activity score did not change significantly during follow-up., Conclusion: our results showed that GLP-1 agonists were effective and had a good safety profile in IBD patients. Most adverse effects were mild, and the IBD activity had no significant changes.

Obesity and metabolic syndrome are among the most prevalent health problems in developed countries. The impairment of adipose tissue (AT) function is partially responsible for the aetiology of these conditions. Epigenetics refers to several processes that add modifications to either the DNA or chromatin architectural proteins (histones). These processes can regulate gene expression, chromatin compaction and DNA repair. Epigenetics includes mechanisms by which the cell can adapt the cellular response to the environmental conditions. Here, we review the role of epigenetics in the onset of obesity and related metabolic disorders, with special focus on AT. We highlight the importance of nutrients and lifestyle in the regulation of the epigenetic mechanisms and how they can impact on AT plasticity and function in obesity and metabolic diseases. Thus, the epigenetic landscape emerges as a fine-tune regulator of the cellular responses according to the energetic, metabolic and physiological conditions of the cell. Alterations in metabolic pathways deregulated during obesity and metabolic syndrome could in part explain the disturbances in the epigenetic marks of the AT in these disorders. The understanding of how this epigenetic deregulation may affect AT biology and function could lead to new therapeutic approaches based on epigenetic strategies., (© 2020 World Obesity Federation.)

Objective: This cohort study aimed to explore the relationship between the Notch signaling pathway and the degree of nonalcoholic fatty liver disease (NAFLD). Moreover, this study intended to investigate whether this pathway is related to hepatic lipid metabolism and Toll-like receptors (TLRs)., Methods: This study used real-time polymerase chain reaction analysis to evaluate the hepatic expression level of all genes studied (Notch receptors NOTCH1, NOTCH2, NOTCH3, and NOTCH4, transcription factors HES1 and HES5, and Hes-related repressor proteins HEY1 and HEY2) in hepatic tissue from two cohorts: women with severe obesity (n = 57) and normal liver structure (n = 20) or NAFLD (n = 37)., Results: In women with severe obesity and NAFLD, this study found downregulation of hepatic HES5 expression. This expression correlated positively with the hepatic expression of HES1, HEY1, and NOTCH3. This study also found a positive correlation between HES5 expression and sterol regulatory element-binding protein 1c (SREBP1c) and between NOTCH3 and several genes related to hepatic lipid metabolism (encoding liver X nuclear receptor α variant 1, farnesoid X nuclear receptor, SREBP1c, acetyl-CoA carboxylase 1, fatty acid synthase, peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1, carnitine O-octanoyltransferase, ATP-binding cassette subfamily A member 1, and ATP-binding cassette subfamily G member 1). Finally, this study found a positive correlation between NOTCH2 and TLR2, TLR4, and TLR9 and a positive relationship between NOTCH1 and TLR9., Conclusions: Taken together, these findings suggest that hepatic expression of Notch proteins and ligands in relation to lipid metabolism pathways in the liver could have a role in NAFLD pathogenesis., (© 2020 The Obesity Society.)

Erectile dysfunction (ED), a condition closely related to cardiovascular morbidity and mortality, is frequently associated with obesity. In this study, we aimed to determine the prevalence of ED and evaluate the associated risk factors in a cohort of 254 young (18-49 years) nondiabetic obese (body mass index [BMI] ≥ 30 kg m -2 ) men from primary care. Erectile function (International Index of Erectile Function [IIEF-5] questionnaire), quality of life (Aging Males' Symptoms [AMS scale]), and body composition analysis (Tanita MC-180MA) were determined. Total testosterone was determined using high-performance liquid chromatography-mass spectrometry. Multivariate logistic regression analysis was used to study the factors associated with ED. ED prevalence was 42.1%. Subjects with ED presented higher BMI, waist circumference, number of components of the metabolic syndrome, AMS score, insulin resistance, and a more unfavorable body composition than those without ED. Multivariate logistic regression analysis showed that a pathological AMS score (odds ratio [OR]: 4.238, P < 0.001), degree of obesity (BMI ≥ 40 kg m -2 , OR: 2.602, P = 0.005, compared with BMI 30-34.9 kg m -2 ), high-density lipoprotein (HDL)-cholesterol levels (OR: 0.956, P = 0.004), and age (OR: 1.047, P = 0.016) were factors independently associated with ED. In conclusion, we demonstrate that, in a primary care-based cohort of nondiabetic young obese men, ED affected >40% of subjects. A pathological AMS score, the degree of obesity, and age were positively associated with ED, while elevated HDL-cholesterol levels were inversely associated with the odds of presenting ED. Further prospective studies are needed to evaluate the long-term consequences of ED in this population., Competing Interests: None

Despite the fact that circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) remain unchanged after fat load in healthy lean individuals, PCSK9 has been suggested to have a role in postprandial lipemia regulation in obese individuals. On the other hand, intestinal permeability and endotoxemia have been observed to increase more in obese individuals than in non-obese individuals after a lipid load. This study aimed to analyze the relationship between PCSK9, intestinal permeability, and endotoxemia after a high fat load in obese individuals. We included 39 individuals with morbid obesity. Serum PCSK9 levels, intestinal permeability marker (zonulin), endotoxemia markers (LPS and LBP), and lipid parameters were measured before and after 3 h of fat load. A significant rise in triglycerides, apolipoprotein A1, zonulin, LPS, and LBP, and a significant decline in PCSK9, were observed after a lipid load. Linear regression analysis showed that low-density lipoprotein cholesterol (LDL-C) was independently related to PCSK9 at baseline, whereas both zonulin and LDL-C were independently related to PCSK9 levels after fat load. A relationship between zonulin and PCSK9 levels after fat load in individuals with morbid obesity may exist., Competing Interests: The authors declare no conflict of interest.

Objective: Obesity-associated hypoandrogenemia is increasing in parallel to the obesity epidemic. The prevalence of hypoandrogenemia in nondiabetic young men with obesity is not known. This study aimed to evaluate the prevalence of hypoandrogenemia and associated risk factors in this population., Methods: This cross-sectional study included 266 nondiabetic men < 50 years of age with obesity who were referred from primary care. Total testosterone (high-performance liquid chromatography mass spectrometry), sex hormone-binding globulin, free testosterone (FT), luteinizing hormone (LH), high-sensitivity C-reactive protein, and homeostatic model assessment of insulin resistance were determined. Body composition and erectile function were also assessed. Hypoandrogenemia was defined as FT level < 70 pg/mL., Results: Subnormal FT concentrations were found in 25.6% of participants. Hypoandrogenemia prevalence was different along the BMI continuum, being > 75% in individuals with BMI ≥ 50 kg/m 2 . A multivariate regression analysis indicated that increasing BMI (P < 0.001), age (P = 0.049), and reduced LH levels (P = 0.003) were independent risk factors for hypoandrogenemia., Conclusions: In a primary care-based cohort of nondiabetic young men with obesity, hypoandrogenemia was a very prevalent finding and was directly associated with adiposity. Obesity, age, and reduced LH levels were independent risk factors associated with hypoandrogenemia. Further prospective studies are needed to evaluate the long-term consequences of hypoandrogenemia in this population., (© 2019 The Obesity Society.)

Background: Obesity was established as a relevant modifiable risk factor in the onset and progression of colorectal cancer (CRC). This relationship could be mediated by an epigenetic regulation., Objectives: The current work aimed to explore the effects of excess body weight on the DNA methylation profile of CRC using a genome-wide DNA methylation approach and to identify an epigenetic signature of obesity-related CRC., Methods: Fifty-six CRC-diagnosed patients (50 years) were included in the study and categorized according to their body mass index (BMI) as non-obese (BMI ≤ 25 kg/m 2 ) or overweight/obese (BMI > 25 kg/m 2 ). Data from Infinium 450k array-based methylomes of 28 CRC tumor samples were coupled with information on BMI categories. Additionally, DNA methylation results were validated in 28 CRC tumor samples., Results: The analysis revealed statistically significant differences at 299 CpG sites, and they were mostly characterized as changes towards CpG hypermethylation occurring in the obese group. The 152 identified genes were involved in inflammatory and metabolic functional processes. Among these genes, novel genes were identified as epigenetically regulated in CRC depending on adiposity. ZNF397OS and ZNF543 represented the top scoring associated events that were further validated in an independent cohort and exhibited strong correlation with BMI and excellent and statistically significant efficiency in the discrimination of obese from non-obese CRC patients (area under the curve >0.80; p < 0.05)., Conclusions: The present study identifies a potential epigenome mark of obesity-related CRC that could be useful for precision medicine in the management of this disease taking into account adiposity as a relevant risk factor.

Aim: Laparoscopic gastric plication (LGP) is a bariatric surgical technique based on the anatomical principles of laparoscopic sleeve gastrectomy (LSG), but its effects on the metabolic profile are still uncertain. The aim of our study is to compare the changes in weight, metabolic parameters and gastric histology following intervention by gastric plication (GP) and sleeve gastrectomy (SG) in an experimental model of obesity., Methods: To conduct the study, 32 8-week-old male Sprague-Dawley rats (Charles River®) were fattened by means of a cafeteria diet and randomly assigned to the following experimental groups: group 1: GP (n = 12); group 2: SG (n = 12) and group 3: sham (n = 8)., Results: Unlike the SG group, the GP group attained the weight of the sham group at the end of the experiment (week 16). The GP group continued to eat more cafeteria diet than the SG group. In addition, the SG group achieved better glycaemic control than the GP group. Significantly higher plasma ghrelin levels were observed at week 16 in the GP group than in the SG group (2.29 ± 0.5 vs 1.07 ± 0.4, p < 0.05), which also occurred for the glucagon plasmatic levels (62.71 ± 36.2 vs 24.63 ± 9.3, p < 0.05)., Conclusions: GP is not as effective as SG and cannot be considered a metabolic surgery due to observed hormonal variations. The animals subjected to a GP continued to have a high appetite for the cafeteria diet unlike the animals submitted to an SG. Hormonal mechanisms possibly related to glucagon and ghrelin may be involved in this metabolic response.

Adipose tissue has traditionally only been considered as an energy storage organ. Nevertheless, the importance of this tissue in systemic physiology and, especially, in systemic inflammation has been highlighted in recent years. Adipose tissue expresses proteins related to vitamin D (VD) metabolism, and it has been proposed that it can act as a VD storage tissue. The active form of VD, 1,25-dihydroxyvitamin D3 (1,25(OH)₂D₃), is able to modify adipocyte and adipose tissue physiology via the VD receptor (VDR), decreasing the expression of pro-inflammatory cytokines in adipose tissue. Moreover, VD deficiency and VDR has been reported to be associated with obesity and diabetes. However, the results of the different studies are not conclusive. Insulin growth binding proteins (IGFBPs) have been identified in adipose tissue, but their roles are poorly understood. Therefore, the objective of this study was to analyze the plasma levels of VD and the gene expression of VDR in the adipose tissue of subjects with morbid obesity (MO) and with different degrees of insulin resistance (IR), as well as the functionality of direct interaction between IGFBP-3 and VDR, which could explain its inhibitory role in adipogenesis. Our results show a novel role of the VD system in the regulation and activation of IGFBP-3 in visceral adipose tissue (VAT) of patients with MO, as a new and alternative mechanism proposed in the insulin signaling associated with obesity., Competing Interests: The authors declare no conflict of interest.

Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver disease (NAFLD). We examined the correlation between the circulating levels and hepatic expression of miR122 and miR33a/b*, the key lipid metabolism-related gene expression and the clinicopathological factors of obese women with NAFLD. We measured miR122 and miR33a/b* expression in liver samples from 62 morbidly obese (MO), 30 moderately obese (ModO), and eight normal-weight controls. MiR122 and miR33a/b* expression was analyzed by qRT-PCR. Additionally, miR122 and miR33b* circulating levels were analyzed in 122 women. Hepatic miR33b* expression was increased in MO compared to ModO and controls, whereas miR122 expression was decreased in the MO group compared to ModO. In obese cohorts, miR33b* expression was increased in nonalcoholic steatohepatitis (NASH). Regarding circulating levels, MO patients with NASH showed higher miR122 levels than MO with simple steatosis (SS). These circulating levels are good predictors of histological features associated with disease severity. MO is associated with altered hepatic miRNA expression. In obese women, higher miR33b* liver expression is associated with NASH. Moreover, multiple correlations between miRNAs and the expression of genes related to lipid metabolism were found, that would suggest a miRNA-host gene circuit. Finally, miR122 circulating levels could be included in a panel of different biomarkers to improve accuracy in the non-invasive diagnosis of NASH., Competing Interests: The authors declare no conflict of interest.

The purpose of this work was to evaluate the expression of fatty acid metabolism-related genes in human adipose tissue from moderately obese women. We used qRT-PCR and Western Blot to analyze visceral (VAT) and subcutaneous (SAT) adipose tissue mRNA expression involved in de novo fatty acid synthesis (ACC1, FAS), fatty acid oxidation (PPARα, PPARδ) and inflammation (IL6, TNFα), in normal weight control women (BMI < 25 kg/m², n = 35) and moderately obese women (BMI 30-38 kg/m², n = 55). In SAT, ACC1, FAS and PPARα mRNA expression were significantly decreased in moderately obese women compared to controls. The downregulation reported in SAT was more pronounced when BMI increased. In VAT, lipogenic-related genes and PPARα were similar in both groups. Only PPARδ gene expression was significantly increased in moderately obese women. As far as inflammation is concerned, TNFα and IL6 were significantly increased in moderate obesity in both tissues. Our results indicate that there is a progressive downregulation in lipogenesis in SAT as BMI increases, which suggests that SAT decreases the synthesis of fatty acid de novo during the development of obesity, whereas in VAT lipogenesis remains active regardless of the degree of obesity.

Context: The relationship between 25-hydroxyvitamin D [25(OH)D] and obesity and type 2 diabetes is not completely understood. Vitamin D receptor (VDR) expression in adipose tissue (AT) is related to obesity and might be regulated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]., Objective: To analyze serum 25(OH)D and VDR gene expression in AT according to body mass index (BMI) and glycemic status and the effect of 1,25(OH)2D3 on AT according to BMI., Design and Patients: Two cohorts were studied: 1) 118 subjects classified according to their BMI (lean, overweight, obese, or morbidly obese [MO]) and their glycemic status (normoglycemic [NG] and prediabetic and diabetic [P&D]); and 2) 30 obese subjects (BMI > 30 kg/m(2)) classified as NG and P&D. VDR gene expression was analyzed during preadipocyte differentiation and in vitro stimulation with 1,25(OH)2D3 of AT explants from donors with different BMI values., Setting: University Hospital., Main Outcome Measures: Serum 25(OH)D, parathyroid hormone (PTH), and AT VDR gene expression., Results: 25(OH)D levels were lower in P&D than NG subjects, significantly so in the lean and MO groups (P < .05). 25(OH)D levels correlated negatively with homeostasis model of assessment for insulin resistance (HOMA-IR) (r = -0.200; P = .032) and glucose (r = -0.295; P = .001), but not with BMI. VDR gene expression was higher in MO than in the other BMI groups (P < .05). 1,25(OH)2D3 increased VDR gene expression in AT from obese patients (P < .05) but not from lean subjects., Conclusions: 25(OH)D levels are diminished in P&D compared to NG subjects, independently of BMI, and are closely related to glucose metabolism variables, suggesting that vitamin D deficiency is associated more with carbohydrate metabolism than with obesity. Moreover, AT has a different response to 1,25(OH)2D3 depending on the degree of obesity.

Background: Low concentrations of plasma vitamin D (25(OH)D) have been associated with the development of metabolic syndrome (MetS), obesity, diabetes and cardiovascular disease. The objective of this study was to quantify the associations between 25(OH)D and parathormone (PTH) plasma levels and obesity, the presence of MetS, diabetes or atherogenic dyslipidemia (AD) in a large sample of individuals with different degrees of adiposity., Methods: Retrospective study of all patients who had attended the obesity clinics in a Spanish hospital between 2009 and 2011, and whose concentrations of PTH, 25(OH)D, calcium and alkaline phosphatase had been determined (n=316, 75.9% women). Individuals were categorized by degree of adiposity, presence of MetS, and other comorbidities., Results: PTH increased but 25(OH)D and calcium decreased with increasing adiposity. The prevalence of 25(OH)D deficiency or insufficiency increased with obesity (<10% when BMI<45kg/m(2), and 26% when >50). The prevalence of hyperparathyroidism increased from 12% in non-obese to 47.5% in morbidly obese individuals with BMI>50 kg/m2. Low plasma 25(OH)D and high PTH concentrations were associated with an increased risk of MetS and AD. These associations disappeared, except in the case of AD for 25(OH)D when adjusting for BMI. Regression analysis revealed that BMI and age or seasonality were independent predictors of PTH and 25(OH)D levels, respectively., Conclusions: BMI was the variable most strongly associated with plasma 25(OH)D and PTH concentrations in our study. Low 25(OH)D and high PTH concentrations were not independently associated with an increased risk of MetS, or diabetes. Our data support a possible contribution of plasma 25(OH)D to the pathogenesis of hypertriglyceridemia and AD through inflammation.

Objective: To compare lipid and lipoprotein concentrations between obese and non-obese women with a diagnosis of polycystic ovary syndrome (PCOS) treated with metformin for 6 months., Methods: Sixty-five women with a diagnosis of PCOS were included. The presence of obesity, serum concentrations of cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were recorded before and after 6 months of metformin treatment. The women were divided in two groups of 34 obese women (group A; body mass index >27 kg/m(2)) and 31 non-obese women (group B; body mass index (<27 kg/m(2))., Results: Significant differences in body mass index, waist-hip ratio, cholesterol, triglycerides, LDL-c and HDL-c were found in group A compared with group B (p<0.05). In obese women, serum triglyceride and LDL-c concentrations were significantly reduced (p<0.05), while serum concentrations of HDL-c were significantly increased (p<0.05) after 6 months of treatment. In non-obese women, none of these lipid profile modifications were considered significant (p=ns)., Conclusion: Metformin use for 6 months modified triglyceride, LDL-c and HDL-c concentrations compared with initial values in obese women with PCOS while no significant modifications in lipid or lipoprotein concentrations were observed in non-obese women., (2010 SEEN. Published by Elsevier Espana. All rights reserved.)

Introduction: Tumor necrosis factor (TNFalpha) has been invoked as an adipostat. Accordingly, the adipose tissue expression of TNFalpha has been shown to be proportional to the degree of adiposity. The regulatory role of TNFalpha in obesity may be controlled by several mechanisms. These include the inhibitory effect on LPL activity, the mediation on glucose homeostasis or the effect on leptin. To assess the role of TNFalpha in obesity we measured adipocyte TNFalpha expression in 96 females with a wide range of adiposity and with or without type 2 diabetes. We analysed the relationship between TNFalpha expression, adipocyte LPL activity, insulin resistance and leptin in this population., Results: The TNFalpha and leptin expression of the adipose tissue in obese and morbid obese patients were significantly higher than in controls. Obese and morbid obese patients had slightly higher levels of LPL activity, but these differences were not significant. We observed a significant relationship between adipose TNFalpha expression and body mass index (r=0.35, P<0.001). TNFalpha expression was negatively related to LPL activity (r=-0.28, P<0.05) and positively related to leptin expression (r=0.35, P<0.001)., Conclusion: Our results indicate that obese women, even those with morbid obesity, over-express TNFalpha in subcutaneous adipose tissue in proportion to the magnitude of the fat depot and independently of the presence of type 2 diabetes. The TNFalpha system may be a homeostatic mechanism that prevents further fat deposition by regulating LPL activity and leptin production.

Background: Lipocalin 2 (LCN2) has been related to obesity, insulin resistance and metabolic disturbance. However, its relation with non alcoholic fatty liver disease (NAFLD) has hardly been studied. Methods: We examined LCN2 circulating levels and its protein and gene expression in liver from women with severe obesity and NAFLD. We analyzed the liver histology of 59 white severely obese women (BMI ⩾ 40 Kg/m2 ): 15 subjects presented normal liver histology or non-significant liver disease (NL), 18 simple steatosis (SS) and 26 non alcoholic steatohepatitis (NASH). We determined the anthropometric and metabolic features of the women. LCN2 levels were determined by an ELISA and liver mRNA expression by real time RT-PCR. We also studied LCN2 expression in HepG2 liver cells under various inflammatory stimuli. Results: Liver LCN2 protein and gene expression were higher in NAFLD than in obese with NL. Liver LCN2 gene expression correlated with SS (r = 0.351, p = 0.016), and its protein expression correlated with NASH (r = 0.705, p = 0.003). LCN2 expression was detected in HepG2 cells after the administration of TNFα, IL6, resistin or adiponectin. LCN2 expression was induced by TNFα, IL6 and resistin. Conclusions: Liver LCN2 is related to NAFLD in severely obese women. Up-regulation of LCN2 expression is detected in HepG2 cells after exposure to TNFα, IL6 and resistin. These results suggest that LCN2 expression is induced under liver harmful conditions. [ABSTRACT FROM AUTHOR]

Context:It has been suggested that weight loss can improve systemic inflammation associated with obesity by decreasing the adipose production of pro-inflammatory cytokines. This suggestion, however, remains controversial.Objective:To analyse the effect of weight loss on peripheral inflammatory markers and subcutaneous adipocytokine production.Design:Patients were studied at baseline, at the end of the weight loss period, and after 2 weeks of weight stabilisation.Subjects:Nineteen morbid obese non-diabetic patients and 20 lean control subjects.Intervention:During the weight loss period patients followed a 6-week low-calorie diet.Measurements:Plasma levels of inflammatory markers, maximal in vitro whole-blood cytokine production, subcutaneous adipose tissue expression and content of several cytokines.Results:Obese subjects had higher circulating levels of C reactive protein (CRP), serum amyloid A (SAA), interleukin IL-6, IL-1 and soluble tumor necrosis factor receptors (sTNFR). Weight loss was associated with a significant decrease in CRP, SAA, leucocytes and plasma IL-6. Maximal in vitro cytokine production of IL-1 and sTNFR1 increased during this period. Weight loss did not induce significant changes in the adipose concentrations of IL-6, IL-1 or sTNF-receptors. However, adipose expression of IL-6, IL-1, TNFα, membrane cofactor protein-1 and adiponectin increased at the end of the weight loss period. During weight maintenance, circulating inflammatory parameters increased and in some cases returned to baseline.Conclusions:A low-calorie diet is associated with an improvement in the systemic inflammatory status. This seems to be due to energy restriction rather than to adipose mass loss, since inflammatory levels return to baseline soon after weight stabilisation. Furthermore, a negative energy balance and fat mobilisation are associated with increased subcutaneous cytokine adipose expression.International Journal of Obesity (2006) 30, 1714–1720. doi:10.1038/sj.ijo.0803348; published online 25 April 2006 [ABSTRACT FROM AUTHOR]