Energy balance and hypothalamic effects of a high-protein/low-carbohydrate diet

Diets high in fat or protein and extremely low in carbohydrate are frequently reported to result in weight loss in humans. We previously reported that rats maintained on a low-carbohydrate–high fat diet (LC–HF) consumed similar kcals/day as chow (CH)-fed rats and did not differ in body weight after 7 weeks. LC–HF rats had a 45% decrease in POMC expression in the ARC, decreased plasma insulin, and increased plasma leptin and ghrelin. In the present study we assessed the effects of a low-carbohydrate–high-protein diet (HP: 30% fat, 65% protein, and 5% CHO) on body weight, caloric intake, plasma hormone levels and hypothalamic gene expression. Male rats (n = 16) were maintained on CH or HP for 4 weeks. HP rats gained significantly less weight than CH rats (73.4 +/− 9.4 and 125.0 +/− 8.2 g) and consumed significantly less kcals/day (94.8 +/− 1.5 and 123.6 +/− 1.1). Insulin was significantly reduced in HP rats (HP: 1.8 +/− 0.6 vs. CH: 4.12 +/− 0.8 ng/ml), there were no differences between groups in plasma leptin and plasma ghrelin was significantly elevated in HP rats (HP: 127.5 +/− 45 vs. CH: 76.9 +/− 8 pg/ml). Maintenance on HP resulted in significantly increased ARC POMC (HP: 121 +/− 10.0 vs. 100 +/− 5.9) and DMH NPY (HP: 297 +/− 82.1 vs. CH: 100 +/− 37.7) expression compared to CH controls. These data suggest that the macronutrient content of diets differentially influences hypothalamic gene expression in ways that can affect overall intake.