50. BRANCHED CHAIN AMINO ACID CATABOLISM SUPPORTS ADIPOCYTE DIFFERENTIATION AND LIPOGENESIS
Name: Courtney Renee Green
Grad Year: 2019
The overall goal of my research is to understand the metabolism of adipose tissue. Adipose tissue plays important roles in regulating carbohydrate and lipid homeostasis, though less is known about the regulation of amino acid metabolism in adipocytes. Stable isotope tracing and analysis via gas chromatography-mass spectrometry is utilized in our lab to understand cellular metabolism. I applied isotope tracing to pre-adipocytes and differentiated adipocytes to quantify the contributions of different substrates to tricarboxylic acid metabolism and lipogenesis. In contrast to proliferating cells that use glucose and glutamine for acetyl?coenzyme A (AcCoA) generation, differentiated adipocytes increased branched chain amino acid (BCAA) catabolic flux such that leucine and isoleucine from culture media and/or protein catabolism accounted for as much as 30% of lipogenic AcCoA pools. We also found that vitamin B12 deficiency in the culture medium caused methylmalonic acid accumulation and odd-chain fatty acid synthesis. B12 supplementation reduced these metabolites and altered the balance of substrates entering mitochondria. Recently we showed that inhibition of BCAA catabolism through BCKDH knock down compromised adipogenesis. These results quantitatively highlight the contribution of BCAAs to adipocyte metabolism and suggest that BCAA catabolism plays a functional role in adipocyte differentiation. This research is now exploring a number of avenues, namely understanding why BCAA catabolism is necessary for adipocyte differentiation as well as probing adipocyte metabolism in the presence of inflammatory factors as occurs in obese adipose tissue.
Industry Application Area(s)
Life Sciences/Medical Devices & Instruments | Pharmaceutical