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J Vet Med Sci. 2019 May 11;81(5):646-652. doi: 10.1292/jvms.19-0036. Epub 2019 Mar 15.

Activin E enhances insulin sensitivity and thermogenesis by activating brown/beige adipocytes.

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Faculty of Veterinary Medicine, Kitasato University, School of Veterinary Medicine, Towada, Aomori 034-8628, Japan.
Laboratory of Neuropathology, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
Division of Biomedical Sciences, Stem Cell Technology Laboratory, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Ikoma, Nara 630-0192, Japan.
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwakecho, Kyoto 606-8502, Japan.


Activin E, a secreted peptide encoded by the inhibin/activin βE subunit gene, is a member of the transforming growth factor-β superfamily, which is predominantly expressed in the liver. Recent reports have suggested that activin E plays a role in energy homeostasis as a hepatokine. Here, using transgenic mice overexpressing activin E under the control of the β-actin promoter, we demonstrate that activin E controls energy metabolism through brown/beige adipocytes. The glucose tolerance test and insulin tolerance test showed that the insulin sensitivity was improved in the transgenic mice. Furthermore, the mice had a high body temperature compared with wild-type mice. The transgenic brown adipose tissue and mesenteric white adipose tissue showed upregulation of uncoupling protein 1, which enables energy dissipation as heat by uncoupling oxidative phosphorylation from ATP production. Present results indicate that activin E activates energy expenditure through brown/beige adipocyte activation, suggesting that activin E has high potential for obesity therapy.


INHBE; UCP1; browning/beiging; hepatokine; thermogenesis

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