Short-term leptin treatment increases fatty acids uptake and oxidation in muscle of high fat–fed rats

Abstract

The purpose of this study was to measure the effects of short-term (10 days) leptin treatment on insulin sensitivity as it pertains to fatty acid (FA) uptake, oxidation, and muscle triglyceride (mTG) synthesis in animals that have been administered a high-fat (HF) diet for 3 months. Male Wistar rats were randomly assigned to 1 of 4 groups. One group was fed a control diet (CON) and 3 groups were fed a HF diet. The HF and HF-leptin (HF-LEP) groups were fed the HF diet ad libitum and the amount of food eaten by the HF–pair fed (HF-P) group was equal to that of the HF-LEP group. At the end of the dietary period, rats were injected daily either with saline (CON, HF, HF-P) or with leptin (HF-LEP; 10 mg · kg −1 · d −1) for 10 days before hindlimb perfusion. The perfusate contained 600 μmol/L palmitate traced with [ 14C]palmitate, 9 mmol/L glucose, and 100 μU/mL insulin. As dictated by the protocol, energy expenditure was not significantly different ( P > .05) between HF-LEP and HF-P. Palmitate uptake and oxidation as well as mTG synthesis were greater ( P < .05) in HF (9.8 ± 0.3, 2.0 ± 0.1, and 1.9 ± 0.2 nmol · min −1 · g −1) than in CON (8.0 ± 0.4, 1.4 ± 0.1, and 1.1 ± 0.1 nmol · min −1 · g −1) and this was associated with higher levels of mTG in HF. Palmitate uptake and oxidation were higher ( P < .05) in HF-LEP (10.3 ± 0.6 and 2.0 ± 0.1 nmol · min −1 · g −1) than in HF-P (8.3 ± 0.5 and 1.5 ± 0.2 nmol · min −1 · g −1, P < .05), but mTG synthesis and mTG levels were not changed significantly by leptin treatment ( P > .05). High-fat feeding decreased glucose uptake by 41% when compared with CON (2.4 ± 0.4 vs 4.1 ± 0.4 μmol · h −1 · g −1; P < .05) but pair feeding alone (4.7 ± 0.4 μmol · h −1 · g −1) or leptin treatment (3.8 ± 0.3 μmol · h −1 · g −1) similarly prevented the HF diet–induced decrease in glucose uptake. These data indicate that short-term leptin treatment in HF-fed rats alters muscle FA metabolism by increasing FA uptake and oxidation relative to pair feeding alone. This results in a decrease in the FA esterification-oxidation ratio.