title: Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans.
abstract: Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 ± 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance.
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA tmclaugh@stanford.edu.
authors.forename: Tracey
authors.initials: T
authors.lastname: McLaughlin
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Craig
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Li-Fen
authors.initials: LF
authors.lastname: Liu
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Dalia
authors.initials: D
authors.lastname: Perelman
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Candice
authors.initials: C
authors.lastname: Allister
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Spielman
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Cushman
mesh_terms: D050154:Adiposity; D000328:Adult; D015992:Body Mass Index; D048429:Cell Size / Q000187:drug effects; D015331:Cohort Studies; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006963:Hyperphagia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D050177:Overweight / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015430:Weight Gain
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin