The cell biology of fat expansion

Rutkowski, Joseph M.; Stern, Jennifer H.; Scherer, Philipp E.

doi:10.1083/jcb.201409063

Cited by 462 publications

(437 citation statements)

References 164 publications

(216 reference statements)

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“…Therefore, despite the insulin resistance, fat expansion in the obese provides a sink for glucose, which would otherwise accumulate in the bloodstream and further impair glucose tolerance. The converse problem, namely, the inability of adipose tissue to expand, is also conducive to reduced glucose tolerance and dyslipidemia (21).…”

Section: Resultsmentioning

confidence: 99%

Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes

et al. 2015

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OBJECTIVEWe investigated fat distribution and tissue-specific insulin-stimulated glucose uptake (GU) in seven fat compartments (visceral and subcutaneous) and skeletal muscle in morbidly obese patients with (T2D) and without (ND) type 2 diabetes before and 6 months after bariatric surgery. RESEARCH DESIGN AND METHODSA total of 23 obese patients (BMI 43.0 6 3.6 kg/m 2 ; 9 T2D and 14 ND) were recruited from a larger, randomized multicenter SLEEVEPASS study. MRI (for fat distribution) and [18 F]-fluorodeoxyglucose PET (for GU) studies were performed for the obese patients before and 6 months postsurgery; 10 lean subjects served as control subjects and were studied once. RESULTSAt baseline, visceral fat GU was 30 6 7% of muscle GU in control subjects and 57 6 5% in obese patients. Visceral and deep subcutaneous fat were more abundant (despite same total fat mass) and less insulin sensitive in T2D than ND; in both, GU was impaired compared with control subjects. Postsurgery, visceral fat mass decreased (∼40%) more than subcutaneous fat (7%). Tissue-specific GU was improved, but not normalized, at all sites in T2D and ND alike. The contribution of visceral fat to whole-body GU was greater in T2D than ND but decreased similarly with surgery. Subcutaneous fat made a fourfold greater contribution to whole-body GU in obese versus lean subjects (15% vs. 4%) both before and after surgery. CONCLUSIONSBariatric surgery leads to sustained weight loss and improves tissue-specific glucose metabolism in morbidly obese patients. We conclude that 1) enhanced visceral fat accumulation is a feature of T2D, 2) severe obesity compromises muscle insulin sensitivity more than fat insulin sensitivity, and 3) fat mass expansion is a sink for plasma glucose.Visceral fat (VF) and subcutaneous fat (SC) are structurally, metabolically, and functionally distinct, albeit both contribute to obesity (1). Abdominal SC fat has clearly defined, metabolically distinct deep and superficial layers separated by the Scarpa fascia (2,3). Research suggests that the deep layers are metabolically more active

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Section: Resultsmentioning

confidence: 99%

Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes

et al. 2015

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“…Moreover, visceral obesity and the consequent adipose metabolic dysfunction represent important risk factors for the development and progression of NAFLD [43,44]. Obesity may lead to an imbalanced production of pro-and antiinflammatory adipokines secreted from adipose tissue, which contributes to the pathogenesis of NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Association between hemoglobin glycation index and hepatic steatosis in non-diabetic individuals

Fiorentino

Marini

Succurro

et al. 2017

Diabetes Research and Clinical Practice

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Hemoglobin glycation indexHepatic steatosis Non-enzymatic protein glycation A B S T R A C TAims: Hemoglobin glycation index (HGI), which is the difference between the observed value of HbA1 and the predicted HbA1c based on plasma glucose levels, represents a measure of the degree of non-enzymatic glycation of hemoglobin and it has been found to be positively associated with diabetic complications. Herein we investigated whether HGI is associated with hepatic steatosis and related biomarkers in subjects without diabetes.Methods: 1120 White individuals without diabetes were stratified in quartiles according to HGI levels. Hepatic steatosis was diagnosed by ultrasonography.Results: As compared with subjects in the lowest quartile of HGI those in the intermediate and high HGI groups displayed an unfavorable cardio-metabolic risk profile having significantly higher values of body mass index (BMI), waist circumference, % fat mass, total cholesterol, triglycerides, inflammatory markers such as high sensitivity C reactive protein, erythrocytes sedimentation rate, complement C3, platelets and white blood cell count, hepatic insulin resistance assessed by the liver IR index and lower concentrations of highdensity lipoprotein. HGI was positively associated with the biomarker of liver damage alanine aminotransferase, and fatty liver index, an indicator of hepatic steatosis. In a logistic regression analysis adjusted for age, gender and BMI individuals in the highest quartile of HGI exhibited a 1.6-fold increased odd of having hepatic steatosis (95% CI: 1.03-2.41; p = 0.03) as compared with subjects in the lowest quartile of HGI.Conclusions: Higher levels of HGI may identify subjects without diabetes at increased risk of having hepatic steatosis.

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“…Silencing FoxO1 can potently reduce autophagy activity and FSP27 level, suppressing adipocyte differentiation and LD growth. Given that LD expansion contributes to adipocyte hypertrophy and adipose expansion, 6,29,45 further study targeting the FoxO1-autophagy axis may result in therapeutic options to treat obesity.…”

Section: Discussionmentioning

confidence: 99%

“…[38][39][40][41][42] We and others found that FoxO1 also regulated adipogenesis, 3,43,44 a process which may promote adipose expansion via hyperplasia. 6,29,45 Moreover, aberrant adiposity may result from adipocyte or LD hypertrophy. 29,45 In this study, we showed for the first time that FoxO1 regulated LD size and number via an autophagy-FSP27 axis.…”

Section: Discussionmentioning

confidence: 99%

“…6,29,45 Moreover, aberrant adiposity may result from adipocyte or LD hypertrophy. 29,45 In this study, we showed for the first time that FoxO1 regulated LD size and number via an autophagy-FSP27 axis. Given that FoxO1 is activated by insulin resistance 20,46,47 , the FoxO1-autophagy-FSP27 axis may promote LD and adipocyte expansion in obese insulin resistant subjects, thereby casting light on the pathological relevance of augmented autophagy in adipose tissues from obese subjects.…”

Section: Discussionmentioning

confidence: 99%

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FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes

et al. 2016

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Obesity and related metabolic disorders constitute one of the most pressing heath concerns worldwide. Increased adiposity is linked to autophagy upregulation in adipose tissues. However, it is unknown how autophagy is upregulated and contributes to aberrant adiposity. Here we show a FoxO1-autophagy-FSP27 axis that regulates adipogenesis and lipid droplet (LD) growth in adipocytes. Adipocyte differentiation was associated with upregulation of autophagy and fat specific protein 27 (FSP27), a key regulator of adipocyte maturation and expansion by promoting LD formation and growth. However, FoxO1 specific inhibitor AS1842856 potently suppressed autophagy, FSP27 expression, and adipocyte differentiation. In terminally differentiated adipocytes, AS1842856 significantly reduced FSP27 level and LD size, which was recapitulated by autophagy inhibitors (bafilomycin-A1 and leupeptin, BL). Similarly, AS1842856 and BL dampened autophagy activity and FSP27 expression in explant cultures of white adipose tissue. To our knowledge, this is the first study addressing FoxO1 in the regulation of adipose autophagy, shedding light on the mechanism of increased autophagy and adiposity in obese individuals. Given that adipogenesis and adipocyte expansion contribute to aberrant adiposity, targeting the FoxO1-autophagy-FSP27 axis may lead to new anti-obesity options.

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The cell biology of fat expansion

Cited by 462 publications

References 164 publications

Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes

Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes

Association between hemoglobin glycation index and hepatic steatosis in non-diabetic individuals

FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes

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