title: Induction of triglyceride accumulation and mitochondrial maintenance in muscle cells by lactate.
abstract: Muscle exercise induces intramuscular triglyceride (TG) accumulation and promotes mitochondrial maintenance in myotubes. However, the mechanism underlying exercise effects remains unknown. In this study, lactic acid was tested as a signaling molecule in C2C12 myotubes to understand the mechanism. Intracellular TG storage was induced in the cells by sodium lactate. The lactate activity was observed with an inhibition of the cAMP-PKA pathway as indicated by a reduction in the phosphorylation status of CREB (pCREB). Induction of pCREB signal by forskolin was blocked by pretreatment of cells with lactate. The impact of lactate on mitochondrial function was examined with a focus on the activities of two enzymes, MCAT (malonylCoA:ACP transferase) and PDH (pyruvate dehydrogenase). The enzyme activities were induced in the cells by lactate. Expression of the lactate receptor (GPR81) and lactate transporters (MCT1/4) were induced as well by lactate. The lactate activities were observed at concentrations between 4-64 mM, and were not dependent on the increase in intracellular pyruvate. Pyruvate treatment did not generate the same effects in the cells. Those results suggest that lactate may induce intramuscular TG storage and mitochondrial maintenance in myotubes through inhibition of the cAMP pathway by activation of GPR81 in a positive feedback manner.
authors.affiliation: Sport Science College of Beijing Sport University, Beijing, China.|Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University, Louisiana, USA.
authors.forename: Jingquan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University, Louisiana, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Ye
authors.affiliation: China Institute of Sports Medicine, Beijing, China.
authors.forename: Minhao
authors.initials: M
authors.lastname: Xie
authors.affiliation: Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University, Louisiana, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Ye
mesh_terms: D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019344:Lactic Acid / Q000494:pharmacology*; D051379:Mice; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D009124:Muscle Proteins; D014280:Triglycerides; D019344:Lactic Acid; D017868:Cyclic AMP-Dependent Protein Kinases