title: 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 micromol/L palmitate traced with [14C]palmitate, 9 mmol/L glucose, and 100 microU/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 micromol.h-1.g-1; P<.05) but pair feeding alone (4.7+/-0.4 micromol.h-1.g-1) or leptin treatment (3.8+/-0.3 micromol.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.
authors.affiliation: Department of Kinesiology, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Todd
authors.forename: Ben B
authors.initials: BB
authors.lastname: Yaspelkis
authors.forename: Lorraine P
authors.initials: LP
authors.lastname: Turcotte
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D004041:Dietary Fats / Q000493:pharmacokinetics*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004951:Esterification / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D010168:Palmitates; D014280:Triglycerides