Impact of Branched Chain Amino Acids and Cold Exposure on Liver and Adipose Metabolism

Abstract

Branched chain amino acids (BCAAs; Valine, Leucine, Isoleucine) are the primary regulators of tissue protein synthesis. However, higher plasma BCAAs and defects in their degradation coexist with disorders of lipid metabolism during insulin resistance and NAFLD. On the contrary, BCAAs have also been shown to induce mitochondrial lipid oxidation and lower lipid synthesis in insulin sensitive livers. I used cold exposure as a stimulus to amplify the impact of BCAAs on lipid metabolism in the liver and adipose tissue. I hypothesized that in insulin sensitive mice, cold exposure + BCAAs, will prime the liver to induce mitochondrial metabolism while also priming the adipose tissue for adipogenesis. Male mice (C57BL/6NJ) were assigned to four treatments for 2-wks: 1) no BCAAs, room temp; NR, 2) BCAAs in water, room temp; BR, 3) no BCAAs, cold exposed for 5-hrs 10℃; NC, 4) BCAAs in water, cold exposed for 5-hrs 10℃; BC. All mice were given 13C6 leucine in drinking water, for 24-hrs, prior to sacrifice for blood and tissue collection. Western blots of the liver tissue revealed that BCAA degradation (lower pBCKDH/ BCKDH ratio), lipid oxidation (CPT1A), and mitochondrial function (COXIV) proteins were higher in BCAA enriched groups. Tissue histology (H&E) showed no significant differences in lipid accumulation. Gas chromatography-mass spectrometry analysis of plasma 13C6 leucine showed higher enrichment of 13C6 leucine and its keto acid in both BR and BC groups. These results suggest that BCAA supplementation + cold exposure can be a good strategy to amplify the impacts of BCAAs on mitochondrial lipid metabolism, during insulin sensitivity and NAFLD.