Chronic central leptin treatment increases protein intake in rats.

Abstract

Leptin reduces body fat selectively, sparing body protein. Accordingly, during chronic leptin administration, food intake is suppressed and body weight is reduced until body fat is depleted. Body weight then stabilizes at this fatless level while food intake increases to normal caloric levels, presumably in defense of lean body mass. This study evaluates food intake and macronutrient selection during this “fatless” phase of leptin treatment. Male Sprague-Dawley rats were maintained on standard pelleted rodent chow and injected daily with leptin (2.5 μg/3 μl, lateral ventricle) or vehicle solution (3 μl aCSF) until body weight reached a nadir and food intake returned to normal levels. Injections were then continued for 13 days, during which rats self-selected their daily diet from separate sources of carbohydrate (corn meal), protein (casein plus 0.6% methionine), and fat (corn oil). Despite similar caloric intakes on self-selection days 3–13, macronutrient choice differed profoundly in leptin and control rats. Leptin rats ate significantly more protein beginning on day 3, with intakes stabilizing between 45 and 55% of daily kcal. Controls preferred carbohydrate, eating almost no protein until day 10, then gradually increasing protein intake to about 20% of total kcals. Fat intake was stable at approximately 20% of total kcal in both groups. Sustained leptin-induced suppression of body fat stores may increase the utilization of protein for maintenance of energy homeostasis, promoting protein appetite. This protein appetite may contribute to the restoration (or derepression) of food intake that eventually occurs during chronic leptin treatment.