Food Restriction is Required to Preserve the Antisteatotic Effects of Central Leptin in the Liver of Middle-Aged Rats.

Abstract

Aging is a significant risk factor for the development of obesity and hepatic steatosis associated with insulin and leptin resistance. Food restriction (FR) is commonly used for reducing body weight (BW), adiposity, and liver steatosis. Thus, this study aimed to determine whether FR in middle-aged rats can recover the central leptin antisteatotic effects observed in the liver in young animals. Two groups of 4-month-old Wistar rats were fed ad libitum (AL) or were on FR for 3 months. At 7 months of age, both groups were centrally treated with rat leptin (0.2 μg/d, 7 days) or saline. Central leptin reduced food intake and BW, but not the hepatic triglyceride content, in 7-month-old rats fed AL. However, in 7-month-old FR rats, leptin did not affect BW but markedly reduced serum leptin, serum and hepatic triglyceride levels, and the expression of hepatic lipogenic genes. In addition, central leptin decreased serum and hepatic endogenous norepinephrine levels of FR rats, exerting a homeostatic effect beyond its antisteatotic actions. These findings suggest that in middle-aged rats, moderate FR is required for both preserving the antisteatotic actions of central leptin and avoiding excessive weight loss.