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Endocrine Abstracts (2018) 56 GP159 | DOI: 10.1530/endoabs.56.GP159

ECE2018 Guided Posters Obesity (13 abstracts)

Role of Elovl6 in the thermogenic action of brown and beige adipocyte during β3-adrenergic receptor activation

Rahul Sharma 1 , Takashi Matsuzaka 1 , Kaori Motomura 1 , Zao Hui 1 , Hiroshi Ohno 1 , Yoshinori Takeuchi 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.


Recent studies suggest that adult humans have active brown or beige adipocytes, the activation of which might be a therapeutic strategy for the treatment of metabolic diseases. Treatment of CL-316243, a β3-adrenergic receptor agonist, activates brown/beige adipocytes and can cause significant reductions in adiposity. 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 into C18 species, in the thermogenic action of brown/beige adipose tissue. We have observed upregulation of Elovl6 in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) of mice treated with CL-316243 as well as cold-expose. 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. CL-316243 induces the expression of genes involved in creatine metabolism and mitochondrial biogenesis in the iWAT of Elovl6 deficient mice. Pharmacological reduction of creatine levels by the treatment of β-guanidinopropionic acid (β-GPA) to Elovl6 KO mice decreases whole-body energy expenditure after administration of CL-316243. Our data suggest that Elovl6-regulated FA chain length is important for brown/beige adipose tissue function and creatine metabolism has an important compensatory role in adipose tissue energy expenditure and thermogenesis during impaired BAT function.

Volume 56

20th European Congress of Endocrinology

Barcelona, Spain
19 May 2018 - 22 May 2018

European Society of Endocrinology 

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