title: Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis.
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.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Green
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Wallace
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California, USA.
authors.forename: Ajit S
authors.initials: AS
authors.lastname: Divakaruni
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, California, USA.|Department of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Phillips
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California, USA.
authors.forename: Anne N
authors.initials: AN
authors.lastname: Murphy
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, California, USA.|Department of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Ciaraldi
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.|Institute of Engineering in Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Metallo
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000235:genetics / Q000378:metabolism; D041721:3T3-L1 Cells / Q000187:drug effects; D000105:Acetyl Coenzyme A / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D050155:Lipogenesis; D051379:Mice; D008969:Molecular Sequence Data; D009765:Obesity / Q000378:metabolism* / Q000601:surgery; D014233:Tricarboxylic Acids / Q000378:metabolism; D014805:Vitamin B 12 / Q000494:pharmacology
chemical_list: D000597:Amino Acids, Branched-Chain; D014233:Tricarboxylic Acids; D000105:Acetyl Coenzyme A; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D014805:Vitamin B 12