Effects of fructose and glucose on plasma leptin, insulin, and insulin resistance in lean and VMH-lesioned obese rats

To determine the influence of dietary fructose and glucose on circulating l eptin levels in lean and obese rats, plasma leptin concentrations were meas ured in ventromedial hypothalamic (VMH)-lesioned obese and sham-operated le an rats fed either normal chow or fructose- or glucose-enriched diets (60% by calories) for 2 wk. Insulin resistance was evaluated by the steady-state plasma glucose method and intravenous glucose tolerance test. In lean rats , glucose-enriched diet significantly increased plasma leptin with enlarged parametrial fat pad, whereas neither leptin nor fat-pad weight was altered by fructose. Two weeks after the lesions, the rats fed normal chow had mar ked greater body weight gain, enlarged fat pads, and higher insulin and lep tin compared with sham-operated rats. Despite a marked adiposity and hyperi nsulinemia, insulin resistance was not increased in VMH-lesioned rats. Fruc tose brought about substantial insulin resistance and hyperinsulinemia in b oth lean and obese rats, whereas glucose led to rather enhanced insulin sen sitivity. Leptin, body weight, and fat pad were not significantly altered b y either fructose or glucose in the obese rats. These results suggest that dietary glucose stimulates leptin production by increasing adipose tissue o r stimulating glucose metabolism in lean rats. Hyperleptinemia in VMH-lesio ned rats is associated with both increased adiposity and hyperinsulinemia b ut not with insulin resistance. Dietary fructose does not alter leptin leve ls, although this sugar brings about hyperinsulinemia and insulin resistanc e, suggesting that hyperinsulinemia compensated for insulin resistance does not stimulate leptin production.