HYPERLEPTINEMIA - AN EARLY SIGN OF JUVENILE OBESITY - RELATIONS TO BODY-FAT DEPOTS AND INSULIN CONCENTRATIONS

Leptin, the OB gene product, is an adipocyte-derived circulating prote in. In several rodent mod els of obesity, such as the db/db mice, fa/f a rats, and ventromedial hypothalamus-lesioned mice, as well as adult obese subjects, leptin mRNA expression and the circulating levels are elevated, suggesting resistance to its action. However, it is unknown whether the rise in leptin concentration occurs early in the natural e volution of human obesity or is a chronic adaptation to the obese stat e. Moreover, whether the distribution of body fat (i.e., visceral vs. subcutaneous abdominal fat) influences circulating leptin levels has n ot been assessed. We have determined in a group of obese and nonobese children and young adults whether leptin levels I) are increased early in the development of obesity, 2) are related to a specific fat depot measured by magnetic resonance imaging, 3) vary during hyperinsulinem ic, euglycemic, and hyperglycemic clamp studies, and 4) are different in males vs. females. In the basal state, leptin levels were elevated in obese children. Children and adults demonstrated a strong positive correlation between leptin concentrations and the subcutaneous fat dep ot (r = 0.84, P < 0.001). Surprisingly, a weaker correlation was found with visceral fat mass (r = 0.59, P = 0.001). Leptin levels remained unchanged under both euglycemic and hyperglycemic hyperinsulinemic con ditions in both obese and nonobese subjects. A pronounced effect of ge nder on leptin levels was also observed. We conclude that, early in th e development of juvenile obesity, leptin concentrations are elevated and are more closely linked to subcutaneous than visceral fat mass. Ac ute increases in insulin concentrations do not affect circulating lept in levels.