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dc.contributor.authorWallace, Martina
dc.contributor.authorGuertin, David A.
dc.contributor.authorMetallo, Christian M.
dc.date2022-08-11T08:09:51.000
dc.date.accessioned2022-08-23T16:46:07Z
dc.date.available2022-08-23T16:46:07Z
dc.date.issued2018-11-01
dc.date.submitted2018-11-29
dc.identifier.citation<p>Nat Chem Biol. 2018 Nov;14(11):1021-1031. doi: 10.1038/s41589-018-0132-2. Epub 2018 Oct 16. <a href="https://doi.org/10.1038/s41589-018-0132-2">Link to article on publisher's site</a></p>
dc.identifier.issn1552-4450 (Linking)
dc.identifier.doi10.1038/s41589-018-0132-2
dc.identifier.pmid30327559
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40818
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractFatty acid synthase (FASN) predominantly generates straight-chain fatty acids using acetyl-CoA as the initiating substrate. However, monomethyl branched-chain fatty acids (mmBCFAs) are also present in mammals but are thought to be primarily diet derived. Here we demonstrate that mmBCFAs are de novo synthesized via mitochondrial BCAA catabolism, exported to the cytosol by adipose-specific expression of carnitine acetyltransferase (CrAT), and elongated by FASN. Brown fat exhibits the highest BCAA catabolic and mmBCFA synthesis fluxes, whereas these lipids are largely absent from liver and brain. mmBCFA synthesis is also sustained in the absence of microbiota. We identify hypoxia as a potent suppressor of BCAA catabolism that decreases mmBCFA synthesis in obese adipose tissue, such that mmBCFAs are significantly decreased in obese animals. These results identify adipose tissue mmBCFA synthesis as a novel link between BCAA metabolism and lipogenesis, highlighting roles for CrAT and FASN promiscuity influencing acyl-chain diversity in the lipidome.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30327559&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://escholarship.org/uc/item/8x01j749
dc.subjectBiochemistry
dc.subjectCellular and Molecular Physiology
dc.subjectEndocrinology
dc.subjectEnzymes and Coenzymes
dc.subjectLipids
dc.subjectMolecular Biology
dc.subjectNutritional and Metabolic Diseases
dc.subjectPathological Conditions, Signs and Symptoms
dc.subjectTissues
dc.titleEnzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues
dc.typeJournal Article
dc.source.journaltitleNature chemical biology
dc.source.volume14
dc.source.issue11
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3625
dc.identifier.contextkey13391898
html.description.abstract<p>Fatty acid synthase (FASN) predominantly generates straight-chain fatty acids using acetyl-CoA as the initiating substrate. However, monomethyl branched-chain fatty acids (mmBCFAs) are also present in mammals but are thought to be primarily diet derived. Here we demonstrate that mmBCFAs are de novo synthesized via mitochondrial BCAA catabolism, exported to the cytosol by adipose-specific expression of carnitine acetyltransferase (CrAT), and elongated by FASN. Brown fat exhibits the highest BCAA catabolic and mmBCFA synthesis fluxes, whereas these lipids are largely absent from liver and brain. mmBCFA synthesis is also sustained in the absence of microbiota. We identify hypoxia as a potent suppressor of BCAA catabolism that decreases mmBCFA synthesis in obese adipose tissue, such that mmBCFAs are significantly decreased in obese animals. These results identify adipose tissue mmBCFA synthesis as a novel link between BCAA metabolism and lipogenesis, highlighting roles for CrAT and FASN promiscuity influencing acyl-chain diversity in the lipidome.</p>
dc.identifier.submissionpathoapubs/3625
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages1021-1031


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