title: Alpha-lipoic acid supplementation reduces mTORC1 signaling in skeletal muscle from high fat fed, obese Zucker rats.
abstract: The mammalian target of rapamycin (mTOR) signaling pathway is hyperactive in liver, adipose and skeletal muscle tissues of obese rodents. Alpha-lipoic acid (αLA) has been well accepted as a weight-loss treatment, though there are limited studies on its effect on mTOR signaling in high-fat fed, obese rodents. Therefore, the goal of this study was to determine mTOR signaling and oxidative protein alterations in skeletal muscle of high-fat fed, obese rats after αLA supplementation. Phosphorylation of the mTOR substrate, eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and eIF4B were significantly reduced (p < 0.05) in muscle from αLA supplemented rats. Activation of AMP-activated protein kinase (AMPK), an mTOR inhibitory kinase, was higher (p < 0.05) in the αLA group. Protein expression of markers of oxidative metabolism, acetyl CoA carboxylase (ACC), cytochrome c oxidase IV (COX IV), peroxisome proliferator-activated receptor (PPAR), and PPAR gamma coactivator 1-alpha (PGC-1α) were significantly higher (p < 0.05) after αLA supplementation compared to non-supplemented group. Our findings show that αLA supplementation limits the negative ramifications of consuming a high fat diet on skeletal muscle markers of oxidative metabolism and mTORC1 signaling.
authors.affiliation: Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, SUNY, 2 Sherman Hall (Office)/5 Sherman Hall (Lab), Buffalo, NY, 14214, USA.
authors.forename: Zhuyun
authors.initials: Z
authors.lastname: Li
authors.forename: Cory M
authors.initials: CM
authors.lastname: Dungan
authors.forename: Bradley
authors.initials: B
authors.lastname: Carrier
authors.forename: Todd C
authors.initials: TC
authors.lastname: Rideout
authors.forename: David L
authors.initials: DL
authors.lastname: Williamson
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements; D003576:Electron Transport Complex IV / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D009765:Obesity / Q000178:diet therapy / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011924:Rats, Zucker; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D008063:Thioctic Acid / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D039642:Eukaryotic Initiation Factors; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010750:Phosphoproteins; C501429:Ppargc1a protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C031799:eIF-4B; D008063:Thioctic Acid; D003576:Electron Transport Complex IV; D002334:Carnitine O-Palmitoyltransferase; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases