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.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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