Long-term regulation of leptin expression is correlated with adipocyte number in obese rats

OBJECTIVE: To investigate long-term regulation of leptin expression in adipose tissues of obese JCR:LA-corpulent rats, which have been shown to overexpress leptin. DESIGN: Manipulation of adipose tissue growth in obese rats by dietary restriction. INTERVENTIONS: Weanling female obese rats were maintained on 1 of 3 diets until 8 months old. One group was allowed to feed ad libitum, the second was pair-fed with lean rats, and the third had food intake restricted to maintain weights equal to those of age-matched lean rats. OUTCOME MEASURES: Body and fat pad weights, leptin messenger RNA (mRNA) levels, and size and number of adipocytes in retroperitoneal fat pads. RESULTS: Adipose tissue mass was increased 6-fold in the obese rats compared with the lean ones, despite equal body weight and intake restriction that was sufficient to impair growth. Although leptin mRNA level was down-regulated by intake restriction, it was still twice as elevated in the obese rats as in the lean ones, and was highly correlated with specific fat pad mass and adipocyte number, but not with size. CONCLUSIONS: These data suggest that leptin expression is correlated with adipocyte number within a fat pad, and that there is inappropriate hepatic de novo synthesis and storage of triacylglycerols in obese rats. A role for leptin in nutrient partitioning is proposed.