title: Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6.
abstract: Although many transcriptional pathways regulating BAT have been identified, the role of lipid biosynthetic enzymes in thermogenesis has been less investigated. Whereas cold exposure causes changes in the fatty acid composition of BAT, the functional consequences of this remains relatively unexplored. In this study, we demonstrate that the enzyme Elongation of Very Long Chain fatty acids 6 (Elovl6) is necessary for the thermogenic action of BAT. Elovl6 is responsible for converting C16 non-essential fatty acids into C18 species. Loss of Elovl6 does not modulate traditional BAT markers; instead, it causes reduced expression of mitochondrial electron transport chain components and lower BAT thermogenic capacity. The reduction in BAT activity appears to be counteracted by increased beiging of scWAT. When beige fat is disabled by thermoneutrality or aging, Elovl6 KO mice gain weight and have increased scWAT mass and impaired carbohydrate metabolism. Overall, our study suggests fatty acid chain length is important for BAT function.
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Chong Yew
authors.initials: CY
authors.lastname: Tan
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: sv234@medschl.cam.ac.uk.
authors.forename: Samuel
authors.initials: S
authors.lastname: Virtue
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bidault
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Dale
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hagen
authors.affiliation: Medical Research Council Human Nutrition Research, Cambridge CB1 9NL, UK; The Department of Biochemistry and the Cambridge Systems Biology Centre, Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. Electronic address: ajv22@medschl.cam.ac.uk.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D022722:Thermogenesis / Q000502:physiology*
chemical_list: C000630968:Elovl6 protein, mouse; D005227:Fatty Acids; D024101:Mitochondrial Proteins; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases
keywords: Elovl6; adaptive thermogenesis; brown adipose tissue; elongase; energy expenditure; fatty acid acyl chain length