1502-P: Adipose Tissue Protein Response and Insulin Sensitivity in Obesity

Abstract

Dysregulation of adipose tissue (AT) lipolysis, a hallmark of obesity and type 2 diabetes, results in elevated postabsorptive and postprandial plasma free fatty acid (FFA) concentrations. This is thought to be due to adipose insulin resistance with regards to anti-lipolysis effects. Alterations in intracellular adipocyte pathways and/or proteins that mediate this phenomenon in humans are poorly understood. To test the hypothesis that impaired insulin signaling is associated with adipose insulin resistance measured whole body insulin sensitivity (the insulin concentration that suppresses palmitate flux by 50% (IC50 FFA)) in 12 lean, 7 lower body obese and 15 upper body obese (n=15) volunteers using a single step hyperinsulinemic-euglycemic clamp. We also measured adipose pAkt/Akt (a measure of insulin signaling) and hormone sensitive lipase (pHSL/HSL) (a measure of lipolysis protein regulation) in biopsies of abdominal and thigh adipose obtained before and during the insulin clamp were measured. Contrary to our hypothesis, there was a positive relationship between IC50 FFA and insulin clamp fold change of pAkt/Akt in thigh samples (ρ = 0.38, p <0.05) and no relationship for abdominal adipose samples. There was good correlation between abdominal and thigh adipose samples in the fractional change in pAkt/Akt in response to insulin clamp (ρ= 0.49, p < 0.01). IC50 FFA was correlated to fractional decrease in HSL phosphorylation in both abdominal (r = 0.36, p< 0.05) and thigh (r = 0.41, p <0.05) Surprisingly, fold changes of pAKT/AKT in response to insulin clamp were positively correlated to fold change of pHSL/HSL in abdominal adipose tissue (ρ= 0.41, p < 0.05) but not thigh samples. In conclusion we found that insulin resistance in adipose is not related to canonical insulin signaling responses but is related to lipase responses. Disclosure K.Lytle: None. M.D.Jensen: Other Relationship; Novo Nordisk, Elsevier. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK40484)