Ablation of the very long chain fatty acid elongase ELOVL3 in mice leads to constrained lipid storage and resistance to diet-induced obesity
2010 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 24, no 11, 4366-4377 p.Article in journal (Refereed) Published
Although saturated and monounsaturated very-long-chain fatty acids (VLCFA) 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 VLCFA mainly in liver, brown and white adipose tissue and in 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, which is associated with, reduced expression of PPARg and its target genes. 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 VLCFA produced by ELOVL3 are indispensable for appropriate synthesis of liver triglycerides, fatty acid uptake and storage in adipose tissue.
Place, publisher, year, edition, pages
2010. Vol. 24, no 11, 4366-4377 p.
IdentifiersURN: urn:nbn:se:su:diva-34391DOI: 10.1096/fj.09-152298ISI: 000283861100024OAI: oai:DiVA.org:su-34391DiVA: diva2:284661