title: The regulation of body fat distribution and the modulation of insulin action.
abstract: Body fat distribution may determine insulin resistance and its metabolic syndrome in humans, independent of obesity. Surgical removal of visceral fat (VF) in obese rats was associated with decreased leptin plasma levels and its gene expression in subcutaneous fat (SC). Chronic leptin treatment to rats decreased VF specifically supporting the role of leptin in determining fat distribution. Surgical removal of selected VF provided direct evidence of improved in vivo insulin action on hepatic glucose production (HGP) by over 2-fold vs sham-operated control. The impact of decreased VF on improved in vivo insulin action was further supported by obtaining similar decreases in VF by treating rats with leptin (Lep), beta3-aderenoreceptor agonist, or by severe caloric restriction (CR). All these three interventions improved insulin action on the modulation of HGP and were mostly attributed to preservation of hepatic glycogen stores. Because free fatty acids (FFA) plasma levels were unchanged, this effect may not be mediated portally by substrates. Improved peripheral insulin sensitivity and glycogen synthesis was demonstrated only in Lep. These data suggest that VF is a major determinant of hepatic insulin action. In obese rats, the ability of leptin to prevent visceral adiposity and its own expression is attenuated. Thus, the failure of leptin to regulate fat distribution and its own secretion suggest that 'leptin resistance' may be a pathologic feature in obesity.
authors: Division of Endocrinology and the Diabetes Research and Training Center, Albert Einstein College of Medicine, New York 10461, USA.
authors: J A
authors: JA
authors: Cases
authors: N
authors: N
authors: Barzilai
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001823:Body Composition; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D009765:Obesity / Q000503:physiopathology*; D051381:Rats
chemical_list: D007328:Insulin