title: Ablation of the very-long-chain fatty acid elongase ELOVL3 in mice leads to constrained lipid storage and resistance to diet-induced obesity.
abstract: Although saturated and monounsaturated very-long-chain fatty acids (VLCFAs) have long been associated with undesirable effects on health, including obesity, heart failure, and atherosclerosis, the physiological role of endogenous synthesis is largely unknown. The fatty acid elongase ELOVL3 is involved in the synthesis of C20-C24 saturated and monounsaturated VLCFAs mainly in liver, brown and white adipose tissue, and triglyceride-rich glands such as the sebaceous and meibomian glands. Here we show that ablation of ELOVL3 leads to reduced adiponectin levels, constrained expansion of adipose tissue, and resistance against diet-induced obesity, a situation that is more exaggerated in female mice. Both female and male knockout mice show reduced hepatic lipogenic gene expression and triglyceride content, a situation that is associated with reduced de novo fatty acid synthesis and uptake. As a consequence, the VLDL-triglyceride level in serum is significantly reduced. Remarkably, despite increased energy expenditure, markedly reduced serum levels of leptin, and increased expression of orexigenic peptides in the hypothalamus, the Elovl3(-/-) mice do not compensate by increased food intake. Thus, these results reveal that C20-C22 saturated and monounsaturated VLCFAs produced by ELOVL3 are indispensable for appropriate synthesis of liver triglycerides, fatty acid uptake, and storage in adipose tissue.
authors.affiliation: Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Damir
authors.initials: D
authors.lastname: Zadravec
authors.forename: Annelie
authors.initials: A
authors.lastname: Brolinson
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Fisher
authors.forename: Claes
authors.initials: C
authors.lastname: Carneheim
authors.forename: Robert I
authors.initials: RI
authors.lastname: Csikasz
authors.forename: Justine
authors.initials: J
authors.lastname: Bertrand-Michel
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.forename: Hervé
authors.initials: H
authors.lastname: Guillou
authors.forename: Mats
authors.initials: M
authors.lastname: Rudling
authors.forename: Anders
authors.initials: A
authors.lastname: Jacobsson
mesh_terms: D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism*; D054392:Adipokines / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001481:Basal Metabolism / Q000235:genetics; D002478:Cells, Cultured; D004032:Diet; D004435:Eating / Q000235:genetics; D000081031:Fatty Acid Elongases; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D050155:Lipogenesis / Q000235:genetics; D008079:Lipoproteins, VLDL / Q000096:biosynthesis / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology* / Q000378:metabolism; D012737:Sex Factors; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood
chemical_list: D054392:Adipokines; D052242:Adiponectin; C000630960:Elovl3 protein, mouse; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases