ECE2017 Guided Posters Obesity (12 abstracts)
Role of Elovl6 in brown and beige adipose tissue during β3-adrenergic receptor activation
Rahul Sharma 1 , Takashi Matsuzaka 1 , Zao Hui 1 , Hiroshi Ohno 1 , Yoshinori Takeuchi 1 , kaori Motomura 1 , Naoya Yahagi 1 , Motohiro Sekiya 1 , Yoshimi Nakagawa 1 , Masafumi Muratani 2 & Hitoshi Shimano 1
1Department of Internal Medicine, Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; 2Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Anti-obesity therapeutics based on increasing the amount of brown fat have received more attention from industry as the biology and regulation of brown fat are better understood than that of beige fat. Cold exposure and treatment with β3 adrenergic receptor agonist are known to activate brown/beige adipose tissue. Many transcriptional pathways regulating brown/beige adipose tissue have been identified, the role of lipid biosynthetic enzymes in brown/beige adipose tissue has been less investigated. In this study, we investigated the role of Elovl6, the enzyme responsible for converting C16 non-essential fatty acids (FAs) into C18 species, in brown/beige adipose tissue. We have observed upregulation of Elovl3, 4, 6 and 7 in BAT and inguinal WAT of mice treated with β3-adrenergic receptor agonist CL-316243 as well as cold-expose. These elongases are responsible for the conversion of C16 FAs into C30 saturated FAs, indicating the relevance of very long chain FAs in the activation process of brown/beige adipose tissue. It was reported that Elovl6 KO mice have impaired mitochondrial function and hence impaired thermogenic capacity of BAT when exposed to cold temperature (Cell Rep. 13:2039, 2015). When exposed to chronic CL-316243 treatment we observed that Elovl6 KO mice compensate its impaired BAT function by increased development of functional beige fat contributing to its increased energy expenditure. Interestingly, these metabolic changes are appearing to be mediated by increased type-2 cytokine signalling and macrophage polarization in the inguinal WAT of Elovl6 KO mice, as per our preliminary results. We have observed increased expressions of markers for cell proliferation (Ki67), macrophage (F4/80, CD68, Itgax-1, Arg-1, Clec-10) in the beige fat of Elovl6 KO mice compared to WT mice stimulated with CL-316243. These results suggest that Elovl6-regulated FA chain length is important for beiging and M2 macrophages are playing a mediator role in beige adipogenesis.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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