The regulation of body fat distribution and the modulation of insulin action

Body fat distribution may determine insulin resistance and its metabolic sy ndrome in humans, independent of obesity. Surgical removal of visceral fat (VF) in obese rats was associated with decreased leptin plasma levels and i ts gene expression in subcutaneous fat (SC), Chronic leptin treatment to ra ts decreased VF specifically supporting the role of leptin in determining f at distribution. Surgical removal of selected VF provided direct evidence o f improved in vivo insulin action on hepatic glucose production (HGP) by ov er P-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, o r by severe caloric restriction (CR). All these three interventions improve d insulin action on the modulation of HGP and were mostly attributed to pre servation of hepatic glycogen stores. Because free fatty acids (FFA) plasma levels were unchanged, this effect may not be mediated portally by substra tes. Improved peripheral insulin sensitivity and glycogen synthesis was dem onstrated 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 vi sceral adiposity and its own expression is attenuated. Thus, the failure of leptin to regulate fat distribution and its own secretion suggest that 'le ptin resistance' may be a pathologic feature in obesity.