Activin E Controls Energy Homeostasis in Both Brown and White Adipose Tissues as a Hepatokine

• Hashimoto, Osamu

• Funaba, Masayuki

• Sekiyama, Kazunari

• Doi, Satoru

• Shindo, Daichi

• Satoh, Ryo

• Itoi, Hiroshi

• Oiwa, Hiroaki

• Morita, Masahiro

• Suzuki, Chisato

• Sugiyama, Makoto

• Yamakawa, Norio

• Takada, Hitomi

• Matsumura, Shigenobu

• Inoue, Kazuo

• Oyadomari, Seiichi

• Sugino, Hiromu

• Kurisaki, Akira

Abstract

Brown adipocyte activation or beige adipocyte emergence in white adipose tissue (WAT) increases energy expenditure, leading to a reduction in body fat mass and improved glucose metabolism. We found that activin E functions as a hepatokine that enhances thermogenesis in response to cold exposure through beige adipocyte emergence in inguinal WAT (ingWAT). Hepatic activin E overexpression activated thermogenesis through Ucp1 upregulation in ingWAT and other adipose tissues including interscapular brown adipose tissue and mesenteric WAT. Hepatic activin E-transgenic mice exhibited improved insulin sensitivity. Inhibin βE gene silencing inhibited cold-induced Ucp1 induction in ingWAT. Furthermore, in vitro experiments suggested that activin E directly stimulated expression of Ucp1 and Fgf21, which was mediated by transforming growth factor-β or activin type I receptors. We uncovered a function of activin E to stimulate energy expenditure through brown and beige adipocyte activation, suggesting a possible preventive or therapeutic target for obesity.

Journal

• Cell Reports

  Cell Reports 25 (5), 1193-1203, 2018-10-30

  Elsevier

Keywords

• activin E
• beige adipocyte
• brown adipocyte
• browning
• hepatokine
• Inhbe
• insulin sensitivity
• nonshivering thermogenesis
• obesity

Details

• CRID: 1050286428479797504
• NII Article ID: 120006894617
• ISSN: 22111247
• DOI: 10.1016/j.celrep.2018.10.008
• HANDLE: 2433/234944
• Web Site: http://repo.lib.tokushima-u.ac.jp/115050
• Web Site: https://api.elsevier.com/content/article/PII:S2211124718315717?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S2211124718315717?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN