Moderate caloric restriction, but not physiological hyperleptinemia per se, enhances mitochondrial oxidative capacity in rat liver and skeletal muscle -: Tissue-specific impact on tissue triglyceride content and AKT activation

The study aimed at determining, in lean tissues from nonobese rats, whether physiological hyperleptinemia with leptin-induced reduced caloric intake and/ or calorie restriction ( CR) per se: 1) enhance mitochondrial- energy metabolism gene transcript levels and oxidative capacity; and 2) reduce triglyceride content. Liver and skeletal muscles were collected from 6- month- old Fischer 344 rats after 1- wk leptin sc infusion ( 0.4 mg/ kg . d: leptin + approximate to 3- fold leptinemia vs. ad libitum- fed control) or moderate CR ( - 26% of those fed ad libitum) in pair- fed animals ( CR). After 1 wk: 1) leptin and CR comparably enhanced transcriptional expression of mixed muscle mitochondrial genes ( P < 0.05 vs. control); 2) CR independently increased ( P < 0.05 vs. leptin- control) hepatic mitochondrial-lipooxidative gene expression and oxidative capacity; 3) hepatic but not muscle mitochondrial effects of CR were associated ( P < 0.01) with increased activated insulin signaling at AKT level ( P < 0.05 vs. leptin- control); 4) liver and muscle triglyceride content were comparable in all groups. In additional experiments, assessing time course of posttranscriptional CR effects, 3- wk superimposable CR ( P < 0.05): 1) increased both liver and muscle mitochondrial oxidative capacity; and 2) selectively reduced muscle triglyceride content. Thus, in nonobese adult rat: 1) moderate CR induces early increments of mitochondrial- lipooxidative gene expression and time- dependent increments of oxidative capacity in liver and mixed muscle; 2) sustained moderate CR alters tissue lipid distribution reducing muscle but not liver triglycerides; 3) mitochondrial- lipid metabolism changes are tissue- specifically associated with hepatic AKT activation; 4) short- term physiological hyperleptinemia has no independent stimulatory effects on muscle and liver mitochondrial-lipooxidative gene expression. Increased lean tissue oxidative capacity could favor substrate oxidation over storage during reduced nutrient availability.