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Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224 and * Department of Metabolic Diseases, Pfizer Central Research, Groton, CT 06340
Leptin, the ob gene product, is released from adipose tissue and likely acts in the central nervous system, particularly within the hypothalamus, to exert many of its effects. Obesity in C57BL/6J ob/ob mice is caused by a mutation in the ob gene resulting in a lack of functional leptin. In this study, we first compared effects of a single intracerebroventricular (ICV) injection of 3 pmol (50 ng) or 60 pmol (1 µg) leptin on food intake and oxygen consumption of lean and ob/ob mice deprived of food for 4 h during the 48-h period postinjection. Injection of 3 pmol leptin minimally lowered food intake in these mice without influencing oxygen consumption. Injection of 60 pmol of leptin rapidly lowered food intake within 30 min in both lean and ob/ob mice, with effects persisting for 24 h. Lean and ob/ob mice treated with leptin consumed 40 and 60% less food, respectively, in 24 h than vehicle-treated controls. Injection of leptin (60 pmol ICV) suppressed food intake of adrenalectomized mice as well (by 25 and 40% in lean mice and by 20 and 68% in ob/ob mice at 3 and 24 h, respectively), indicating that glucocorticoids are not essential for leptin to suppress food intake. Leptin increased oxygen consumption in conditions in which diet-induced thermogenesis was low, i.e., in fed ob/ob mice and in food-deprived lean mice, but not in fed adrenalectomized ob/ob mice or in fed lean mice. ICV injection of 60 pmol leptin along with 230 pmol (2 µg) of neuropeptide Y (NPY) attenuated NPY-induced feeding in ob/ob, but not in lean mice, suggesting an enhanced potential for crosstalk between the leptin and NPY signaling systems in ob/ob mice lacking endogenous leptin. Leptin exerts rapid-onset actions within the central nervous system to coordinate control of food intake and metabolic rate.
Key words: leptin, intracerebroventricular, food intake, metabolic rate, ob/ob mice.
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