Negative regulation of leptin by chronic high-glycemic index starch diet.

The response of plasma leptin to a high-glycemic index (high-GI) starch diet after a short (3 weeks) and prolonged (12 weeks) period was determined in Sprague-Dawley rats. Age-matched rats were fed an identical isocaloric diet except that the carbohydrates were from either mung bean starch (low-GI) or waxy cornstarch (high-GI). After a single test meal of the high-GI starch diet, postprandial plasma glucose (P < .05) and insulin (P < .01) peaks and plasma glucose (P < .014) and insulin (P < .05) areas were higher versus the low-GI starch diet (n = 8 per group). Other age-matched control rats were fed the same diets for a longer period. After 3 weeks, ob mRNA levels were decreased by 50% (P < .005) in the epididymal adipose tissue of high-GI-fed rats versus low-GI-fed rats, without a significant decrease in plasma leptin. After 12 weeks of the high-GI starch diet, both plasma leptin and ob mRNA were decreased by 34% (P < .005) and 41% (P < .05), respectively, compared with the low-GI diet. Both relative epididymal adipose tissue weight (adjusted per 100 g body weight) and total fat mass, as measured by dual-energy x-ray absorptiometry (DEXA), were unchanged by the high-GI starch diet. Basal nonfasting plasma insulin, glucose, and triglycerides were not altered by the high-GI starch diet, whereas free fatty acids were significantly elevated and associated with a trend (P < .13) for increased plasma free glycerol. Plasma leptin levels were negatively correlated with free fatty acid levels (r = .56, P < .05). Despite low leptin, rats fed on the high-GI diet did not increase their food intake, suggesting increased leptin sensitivity. These findings might precede weight gain and the increase in fat mass. Chronic nutritional factors might alter plasma leptin via several overlapping factors independently of energy intake.