Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis
Open accessAbstract
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.
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In differentiated adipocytes, catabolism of branched-chain amino acids accounts for almost a third of cellular acetyl-CoA pools.
“In differentiated adipocytes, catabolism of branched-chain amino acids accounts for almost a third of cellular acetyl-CoA pools (68).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [68]
In normal physiology, myocytes and adipocytes activate mitochondrial BCAA catabolic enzymes to support ATP production during exercise or fasting and differentiation, respectively.
“In normal physiology, myocytes and adipocytes activate mitochondrial BCAA catabolic enzymes to support ATP production during exercise or fasting and differentiation, respectively.46,47”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [47]
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“In differentiated adipocytes, catabolism of branched-chain amino acids accounts for almost a third of cellular acetyl-CoA pools (68).”
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- Authors
- Green, C. R., Wallace, M., Divakaruni, A. S., Phillips, S. A., Murphy, A. N., Ciaraldi, T. P., & Metallo, C. M.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Metallo, Christian M
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2015-11-16
- Volume
- 12
- Issue
- 1
- Pages
- 15-21
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC4684771
- OpenAlex
- W2179192278
- Cited by
- 471
- References
- 51
- Citations by year
- 2026: 23 · 2025: 56 · 2024: 56 · 2023: 51 · 2022: 53 · 2021: 65 · 2020: 53 · 2019: 25 · 2018: 39 · 2017: 29 · 2016: 21
- FWCI
- 14.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (R01CA188652)
- National Institute of Neurological Disorders and Stroke (R01NS087611)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- branched-chain amino acids, adipogenesis, lipogenesis, TCA cycle, preadipocytes, vitamin B12 deficiency, methylmalonic acid, vitamin B12 supplementation, leucine, isoleucine, amino acid metabolism, mitochondrial metabolism
- MeSH terms
- Acetyl Coenzyme A, Adipose Tissue, Amino Acids, Branched-Chain, Animals, Base Sequence, Cell Differentiation, Humans, Molecular Sequence Data, Obesity, Tricarboxylic Acids, Vitamin B 12, Adipocytes, 3T3-L1 Cells, 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide), Lipogenesis, Adipogenesis, Mice
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