Short-term, high-fat diets lower circulating leptin concentrations in rats

Background: Leptin is produced in proportion to body fat mass and can act on the brain to induce satiety and regulate adipose tissue mass; factors other than adipose tissue mass may influence circulating leptin concentrations Objective: We explored the possibility that short-term, moderately high-fat diets induce weight gain by producing inappropriately low circulating leptin concentrations. Design: Female Hooded Wistar rats were fed either a moderately high-fat diet or control diet. Body weight, energy intake, body composition, and fasting plasma leptin were compared after 4 and 14 wk of dietary treatment. Results: After 4 wk, abdominal fat mass was 38% greater in rats fed the high-fat diet than in those fed the control diet (P < 0.01). However, plasma leptin concentrations were 24% lower in animals fed the high-fat diet (P < 0.05), resulting in significantly lower plasma leptin concentrations per unit abdominal fat mass than in control animals (P < 0.005). From 4 to 14 wk, animals fed the high-fat diet gained twice as much weight and consumed 32 kJ/d more than controls (both P < 0.05). At 14 wk, plasma leptin concentrations per unit abdominal fat mass were 27% lower in rats fed the high-fat diet (P = 0.058) and there was a significant negative association between leptin concentrations per unit abdominal fat mass and body weight (r = 0.44, P < 0.05). Conclusions: Ln the short term, a moderately high-fat diet is associated with lower than expected circulating leptin concentrations, which correlate with a higher body weight. A high-fat diet may therefore contribute to weight gain by reducing leptin secretion in adipose tissue.