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Am J Clin Nutr. 2000 Feb;71(2):438-42.

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

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University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.



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.


We explored the possibility that short-term, moderately high-fat diets induce weight gain by producing inappropriately low circulating leptin concentrations.


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.


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).


In 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.

[Indexed for MEDLINE]

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