Emerging evidence highlights that dysfunction of adipose tissue contributes to impaired insulin sensitivity and systemic metabolic deterioration in obese state. Of note, adipocyte hypertrophy serves as a critical event which associates closely with adipose dysfunction. An increase in cell size exacerbates hypoxia and inflammation as well as excessive collagen deposition, finally leading to metabolic dysregulation. Specific mechanisms of adipocyte hypertrophy include dysregulated differentiation and maturation of preadipocytes, enlargement of lipid droplets, and abnormal adipocyte osmolarity sensors. Also, weight loss therapies exert profound influence on adipocyte size. Here, we summarize the critical role of adipocyte hypertrophy in the development of metabolic disturbances. Future studies are required to establish a standard criterion of size measurement to better clarify the impact of adipocyte hypertrophy on changes in metabolic homeostasis.

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<b><i>Background/Aims:</i></b> Roux-en-Y gastric bypass (RYGB) is one of the most effective therapies for morbid obesity, yet some patients who have taken the surgery still undergo insufficient weight loss. Visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index (BAI), and cardiometabolic index (CMI) have been regarded as clinical indicators of adiposity phenotypes that associated closely with obesity-related metabolic diseases. However, no studies have evaluated the relationship between these indexes and weight loss after bariatric surgery. In this prospective study, we aimed to evaluate whether VAI, LAP, BAI, and CMI would predict postoperative weight loss outcomes after RYGB. <b><i>Methods:</i></b> This study included 38 men and 67 women who have undergone RYGB between January 2017 and May 2018 and recorded their %TWL (percent of total weight loss), %EBMIL (percent of excess body mass index loss), %EWL (percent of excess weight loss), anthropometric indices, and biochemical parameters before and 12 months after the surgery. In addition, VAI, LAP, BAI, and CMI were measured with anthropometric measures or lipid profiles using related equations and analyzed with metabolic characteristics. <b><i>Results:</i></b> Subjects with lower BAI (&#x3c;32.54 in men and 37.39 in women) displayed higher %EBMIL and %EWL 12 months after surgery. BAI was independently associated with %EWL 12 months after surgery in both men and women (both <i>p</i> &#x3c; 0.05). The area under the receiver operating characteristic curve for BAI was significantly higher (0.773 in men and 0.818 in women) than VAI, LAP, and CMI. <b><i>Conclusions:</i></b> BAI serves as a reliable surrogate marker of the weight loss outcome after RYGB. The predictivity of adiposity indexes in beneficial outcomes after weight loss therapies is of important referential value for the implementation and optimization of individualized and refined weight loss treatments for obese patients.

Objective: Morphological alterations including adipocyte hypertrophy and fibrosis deposition are important surrogate markers of visceral adipose tissue function, but the relationships between these morphological changes and type 2 diabetes mellitus (T2DM) and impaired insulin sensitivity are poorly defined. Methods: Omental adipose tissue was obtained from 66 individuals with obesity but without T2DM (OB group), 93 individuals with both obesity and T2DM (T2DM group), and 15 individuals with normal BMI and normal glucose tolerance (NGT group). Adipocyte diameter and volume were measured through pathological section analysis. Pericellular and perilobular fibrosis was determined through picrosirius red staining and immunochemistry, while fibrosis-related genes were tested through gene expression and hydroxyproline content. Results: Compared with the NGT and OB groups, individuals from the T2DM group displayed increased adipocyte diameter and volume levels. Increased adipocyte size (diameter and volume) was positively associated with hyperglycemia and insulin resistance and inversely correlated with insulin sensitivity (using the Matsuda whole-body insulin sensitivity index assessment of insulin sensitivity) and β-cell function (disposition index 30 and disposition index 120). The fibrosis levels of the OB group were the highest out of the three groups, whereas the fibrosis levels of T2DM individuals were lower than the OB group but higher than the NGT group. Although fibrosis was negatively correlated with T2DM, fibrosis deposition was not remarkably associated with impaired systemic insulin sensitivity and glucose metabolism. Conclusions: Compared with fibrosis deposition, adipocyte hypertrophy is more closely associated with T2DM and impaired systemic insulin sensitivity.

Purpose. Targeting white adipose tissue (WAT) beiging has been proposed as an effective way to increase thermogenesis and improve glucose metabolism. Neuromedin U (NMU) is a neuropeptide that could increase energy expenditure, while its effects on WAT beiging and glucose homeostasis remain to be investigated. Methods. Male C57BL/6 mice were fed with high fat diet (HFD) to induce obesity and hyperglycemia and then treated with chronic subcutaneous injection of NMU. Body weight and food intake were recorded daily. After 14 days of injection, intraperitoneal glucose tolerance tests and 18F-fluorodeoxyglucose micro-positron emission tomography/computed tomography (18F-FDG micro-PET/CT) scans were conducted. Subcutaneous WAT (sWAT) and interscapular brown adipose tissue were collected for the evaluation of adipocyte size, expression of uncoupling protein 1 (Ucp1), and other thermogenic-related genes. Stromal vascular fraction of subcutaneous WAT was extracted for the measurement of type 2 innate lymphocytes (ILC2s) proportions. Results. Glucose tolerance was markedly improved by peripherally administered NMU. Micro-PET/CT suggested that NMU promoted WAT beiging, which was further confirmed by haematoxylin and eosin (H&E) staining and immunohistochemistry. In diet-induced-obese (DIO) mice, NMU activated thermogenic-related genes in WAT. In addition, NMU stimulated ILC2s in the stromal vascular fraction of WAT. Conclusion. Taken together, our study indicates that peripheral administration of NMU is a potential therapeutic strategy for the promotion of WAT beiging and the improvement of impaired glucose tolerance.

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