Metabolic Fate of Branched‐Chain Amino Acids During Adipogenesis, in Adipocytes From Obese Mice and C2C12 Myotubes
- 28 November 2016
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 118 (4), 808-818
- https://doi.org/10.1002/jcb.25755
Abstract
Branched-chain amino acid (BCAA) catabolism is regulated by the branched-chain aminotransferase (BCAT2) and the branched-chain α-keto acid dehydrogenase complex (BCKDH). BCAT2 and BCKDH expression and activity are modified during adipogenesis and altered in adipose tissues of mice with genetic or diet-induced obesity. However, little is known about how these modifications and alterations affect the intracellular metabolic fate of BCAAs during adipogenesis, in adipocytes from mice fed a control or high-fat diet or in C2C12 myotubes. Here, we demonstrate that BCAAs are mainly incorporated into proteins during the early stages of adipocyte differentiation. However, they are oxidized and incorporated into lipids during the late days of differentiation. Conversely, 92% and 97% of BCAA were oxidized, 1.6% and 6% were used for protein synthesis and 1.2% and 1.5% were incorporated into lipids in adipocytes from epididymal and subcutaneous adipose tissue, respectively. All three pathways were decreased in adipocytes from mice fed a high-fat diet. In C2C12 myotubes, leucine is mainly used for protein synthesis and palmitate is incorporated into lipids. Interestingly, leucine decreased both palmitate oxidation and its incorporation to lipids and proteins; and palmitate increased leucine oxidation and decreased its incorporation to lipids and proteins in a dose-dependent manner. These results demonstrate that BCAA metabolic fate differs between the early and late stages of adipocyte differentiation and in adipocytes from mice fed a control or high-fat diet; and that leucine affects the metabolic fate of palmitate and vice versa in C2C12 myotubes. J. Cell. Biochem. 9999: 1–11, 2016.Keywords
Funding Information
- Consejo Nacional de Ciencia y Tecnología (155949)
This publication has 46 references indexed in Scilit:
- Metabolic Characterization of a Sirt5 deficient mouse modelScientific Reports, 2013
- Protein synthesis rate is the predominant regulator of protein expression during differentiationMolecular Systems Biology, 2013
- Extensive chromatin remodelling and establishment of transcription factor ‘hotspots’ during early adipogenesisThe EMBO Journal, 2011
- Metabolite profiles and the risk of developing diabetesNature Medicine, 2011
- Multi-tissue, selective PPARγ modulation of insulin sensitivity and metabolic pathways in obese ratsAmerican Journal of Physiology-Endocrinology and Metabolism, 2011
- Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels*Online Journal of Public Health Informatics, 2010
- Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitizationProceedings of the National Academy of Sciences of the United States of America, 2009
- A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin ResistanceCell Metabolism, 2009
- Leucine modulation of mitochondrial mass and oxygen consumption in skeletal muscle cells and adipocytesNutrition & Metabolism, 2009
- Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolismAmerican Journal of Physiology-Endocrinology and Metabolism, 2007