Format

Send to

Choose Destination
Nat Chem Biol. 2016 Jan;12(1):15-21. doi: 10.1038/nchembio.1961. Epub 2015 Nov 16.

Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis.

Author information

1
Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
2
Department of Pharmacology, University of California, San Diego, La Jolla, California, USA.
3
Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
4
Department of Medicine, University of California, San Diego, La Jolla, California, USA.
5
Institute of Engineering in Medicine, University of California, San Diego, La Jolla, California, USA.

Abstract

Adipose tissue plays important roles in regulating carbohydrate and lipid homeostasis, but less is known about the regulation of amino acid metabolism in adipocytes. Here we applied isotope tracing to pre-adipocytes and differentiated adipocytes to quantify the contributions of different substrates to tricarboxylic acid (TCA) metabolism and lipogenesis. In contrast to proliferating cells, which use glucose and glutamine for acetyl-coenzyme A (AcCoA) generation, differentiated adipocytes showed increased branched-chain amino acid (BCAA) catabolic flux such that leucine and isoleucine from medium and/or from protein catabolism accounted for as much as 30% of lipogenic AcCoA pools. Medium cobalamin deficiency caused methylmalonic acid accumulation and odd-chain fatty acid synthesis. Vitamin B12 supplementation reduced these metabolites and altered the balance of substrates entering mitochondria. Finally, inhibition of BCAA catabolism compromised adipogenesis. These results quantitatively highlight the contribution of BCAAs to adipocyte metabolism and suggest that BCAA catabolism has a functional role in adipocyte differentiation.

PMID:
26571352
PMCID:
PMC4684771
DOI:
10.1038/nchembio.1961
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center