Dietary restriction in moderately obese rats improves body size and glucose handling without the renal and hepatic alterations observed with a high-protein diet.

Obesity is increasing worldwide, and high-protein (HP) diets are widely used for weight loss. However, the overall safety of HP diets is not well established in obese individuals, who make up a significant proportion of the population. To evaluate the health effects of an HP diet in obesity, obesity-prone (OP) Sprague-Dawley rats were given high-fat diets for 12 weeks to induce obesity. Following this, for 8 more weeks, these rats were given either a normal-protein (NP) (15% of energy) or an HP (35% of energy) diet ad libitum, or the NP diet at a restricted level to achieve body weights similar to those of the HP group (pair-weighted (PW) group). Obesity-resistant (OR) control rats were also given the NP diet throughout the feeding period. The HP-OP group had higher food intake but lower body weight, improved glucose handling, and lowered serum haptoglobin compared with the NP-OP group. These benefits were also observed in PW-OP rats. In addition, PW-OP rats had less fat accumulation when compared with NP-OP rats, and an improved Lee index, lower liver size, and lower serum alanine aminotransferase when compared with HP-OP rats. On the other hand, kidney size, proteinuria, and serum homocysteine were increased in HP-OP rats compared with NP-OP rats, whereas PW-OP rats did not experience these effects. These results indicate that in obese rats, more benefits are obtained via dietary restriction with an NP diet and without some of the potentially detrimental effects of an HP diet.