Effects of high-fat feeding on leptin sensitivity in weanling and adult mice

Abstract

Genetically obese mice exhibit mutations in leptin or its receptor and are inappropriate for studying human obesity, a hyperleptinemic condition with an intact leptin system. High- fat diets reportedly induce resistance to peripherally administered leptin and may better represent obese humans. 35-day-old, C57BL/6J high- fat (45% kcal fat) fed mice housed individually did not decrease food intake or body weight in response to central or peripheral leptin injections. Peripheral infusions of leptin reduced body fat of 35-day-old mice and 15-week-old mice fed high- fat diet but had no effect on adipocyte glycerol or free fatty acid release in adult mice suggesting that leptin reduces body fat by mechanisms other than lipolysis. Group-housing young mice on bedding prevented fat loss in high- fat fed female C57BL/6J mice suggesting that the lipopenic effect of leptin is in part due to increased thermogenesis. These studies suggest the development of leptin resistance is complex and involves additional factors.