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Am J Physiol Endocrinol Metab. 2019 Nov 26. doi: 10.1152/ajpendo.00241.2019. [Epub ahead of print]

Leucine Decreases Intramyocellular Lipid Deposition in an mTORC1-independent Manner in Palmitate-treated C2C12 Myotubes.

Author information

1
Center for Human Nutrition, Department of Food Science, University of Arkansas System Division of Agriculture, Fayetteville, AR, United States.
2
Department of Poultry Science, University of Arkansas System Division of Agriculture, Fayetteville, AR, United States.
3
Department of Animal Science, University of Arkansas System Division of Agriculture, Fayetteville, AR, United States.

Abstract

Higher intramyocellular lipid (IMCL) deposition in skeletal muscle is commonly observed in obese patients, resulting in mitochondrial damage. Palmitic acid (PA), a saturated fatty acid, has been reported to induce obesogenic conditions in C2C12 myotubes. Leucine has been shown to improve obesity-related metabolic signatures, however, evidence for the effect of leucine on IMCL and the underlying mechanisms are still lacking. The objective of this study was to determine the effect of leucine on IMCL deposition and identify the potential mechanisms. Palmitate-treated C2C12 myotubes were used as an in vitro model of obesity. Two doses of leucine were used: 0.5mM (postprandial physiological plasma concentration) and 1.5mM (supraphysiological plasma concentration). Rapamycin was used to determine the role of mTORC1 in leucine's regulation of lipid deposition in C2C12 myotubes. One-way ANOVA followed by Tukey's post hoc test was used to calculate differences between treatment groups. Our results demonstrate that leucine reduces IMCL deposition in a mTORC1-independent fashion. Further, leucine acts independently of mTORC1 to upregulate gene expression related to fatty acid metabolism and works through both mTORC1-dependent and mTORC1-independent pathways to regulate mitochondrial biogenesis in palmitate-treated C2C12 myotubes. In agreement with increased mitochondrial biogenesis, increased mitochondrial content, circularity and decreased autophagy are observed in the presence of 1.5 mM leucine. Taken together, the results indicate leucine reduces IMCL potentially through a mTORC1-independent pathway in palmitate-treated C2C12 myotubes.

KEYWORDS:

leucine; mTORC1; mitochondria; obesity; skeletal muscle

PMID:
31770014
DOI:
10.1152/ajpendo.00241.2019

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