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

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.

• Authors: Osamu Hashimoto, Masayuki Funaba, Kazunari Sekiyama, Satoru Doi, Daichi Shindo, Ryo Satoh, Hiroshi Itoi, Hiroaki Oiwa, Masahiro Morita, Chisato Suzuki, Makoto Sugiyama, Norio Yamakawa, Hitomi Takada, Shigenobu Matsumura, Kazuo Inoue, Seiichi Oyadomari, Hiromu Sugino, Akira Kurisaki
• Journal: Cell reports (Cell Rep) Vol. 25 Issue 5 Pg. 1193-1203 (10 30 2018) ISSN: 2211-1247 [Electronic] United States
• PMID: 30380411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Inhbe protein, mouse
• Transforming Growth Factor beta
• fibroblast growth factor 21
• Activins
• Fibroblast Growth Factors
• Inhibin-beta Subunits
• Activin Receptors, Type I
• Glucose

Topics

• Activin Receptors, Type I (metabolism)
• Activins (metabolism)
• Adipocytes, Beige (metabolism)
• Adipocytes, Brown (metabolism)
• Adipose Tissue, Brown (metabolism)
• Adipose Tissue, White (metabolism)
• Animals
• Body Weight
• Cell Differentiation
• Cold Temperature
• Energy Metabolism
• Fibroblast Growth Factors (metabolism)
• Glucose (metabolism)
• HEK293 Cells
• Homeostasis
• Humans
• Inhibin-beta Subunits (metabolism)
• Insulin Resistance
• Lipid Metabolism
• Liver (metabolism)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Thermogenesis
• Transforming Growth Factor beta (metabolism)