4.1 Article

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

Journal

JOURNAL OF VETERINARY MEDICAL SCIENCE
Volume 81, Issue 5, Pages 646-652

Publisher

JAPAN SOC VET SCI
DOI: 10.1292/jvms.19-0036

Keywords

INHBE; browning/beiging; hepatokine; thermogenesis; UCP1

Funding

  1. Japan Society for the Promotion of Science (JSPS KAKENHI) [JP21580370]
  2. JSPS KAKENHI [JP25640109, JP26450442]

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Activin E, a secreted peptide encoded by the inhibin/activin beta E subunit gene, is a member of the transforming growth factor-beta 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 beta-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.

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