title: Restoration of skeletal muscle leptin response does not precede the exercise-induced recovery of insulin-stimulated glucose uptake in high-fat-fed rats.
abstract: Leptin administration increases fatty acid (FA) oxidation rates and decreases lipid storage in oxidative skeletal muscle, thereby improving insulin response. We have previously shown high-fat (HF) diets to rapidly induce skeletal muscle leptin resistance, prior to the disruption of normal muscle FA metabolism (increase in FA transport; accumulation of triacylglycerol, diacylglycerol, ceramide) that occurs in advance of impaired insulin signaling and glucose transport. All of this occurs within a 4-wk period. Conversely, exercise can rapidly improve insulin response, in as little as one exercise bout. Thus, if the early development of leptin resistance is a contributor to HF diet-induced insulin resistance (IR) in skeletal muscle, then it is logical to predict that the rapid restoration of insulin response by exercise training would be preceded by the recovery of leptin response. In the current study, we sought to determine 1) whether 1, 2, or 4 wk of exercise training was sufficient to restore leptin response in isolated soleus muscle of rats already consuming a HF diet (60% kcal), and 2) whether this preceded the training-induced corrections in FA metabolism and improved insulin-stimulated glucose transport. In the low-fat (LF)-fed control group, insulin increased glucose transport by 153% and leptin increased AMPK and ACC phosphorylation and the rate of palmitate oxidation (+73%). These responses to insulin and leptin were either severely blunted or absent following 4 wk of HF feeding. Exercise intervention decreased muscle ceramide content (-28%) and restored insulin-stimulated glucose transport to control levels within 1 wk; muscle leptin response (AMPK and ACC phosphorylation, FA oxidation) was also restored, but not until the 2-wk time point. In conclusion, endurance exercise training is able to restore leptin response, but this does not appear to be a necessary precursor for the restoration of insulin response.
authors.affiliation: Dept. of Human Health and Nutritional Sciences, Animal Science and Nutrition Bldg., Rm 205, University of Guelph, Guelph, ON, Canada.
authors.forename: Ian R W
authors.initials: IR
authors.lastname: Ritchie
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Gulli
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Stefanyk
authors.forename: Ewa
authors.initials: E
authors.lastname: Harasim
authors.forename: Adrian
authors.initials: A
authors.lastname: Chabowski
authors.forename: David J
authors.initials: DJ
authors.lastname: Dyck
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D004075:Diglycerides / Q000096:biosynthesis / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002518:Ceramides; D004041:Dietary Fats; D004075:Diglycerides; D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D007328:Insulin; D020738:Leptin; D054411:Receptors, Leptin; C495694:Slc2a4 protein, rat; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014280:Triglycerides; D019308:Palmitic Acid; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose