The study aimed at determining, in lean tissues from non-obese rats, whether physiological hyperleptinemia with leptin-induced reduced caloric intake and/or caloric restriction (CR) per se: 1) enhance mitochondrial-energy metabolism gene transcript levels and oxidative capacity; 2) reduce triglyceride content. Liver and skeletal muscles were collected from six-month-old Fischer344 rats following one-week leptin sc infusion (0.4 mg/kg • day: LEP: + threefold leptinemia vs. ad libitum fed Control) or moderate CR (-26% of ad-lib) in pair-fed animals (CR). After one-week: a) LEP and CR comparably enhanced transcriptional expression of mixed muscle mitochondrial genes (P < 0.05 vs. Control); b) CR independently increased (P < 0.05 vs. LEP-Control) hepatic mitochondrial-lipooxidative gene expression and oxidative capacity; c) 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. LEP-Control); d) liver and muscle triglyceride content were comparable in all groups. In additional experiments assessing time-course of post-transcriptional CR effects, three-week superimposable CR (P < 0.05): a) increased both liver and muscle mitochondrial oxidative capacity; b) selectively reduced muscle triglyceride content. Thus in non-obese 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.