Activin E controls energy homeostasis in both Brown and white adipose tissues as a hepatokine
Open accessAbstract
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.
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In mice, activin E is needed to induce thermogenesis by stimulating beige adipocytes in WAT.
“A study in mice showed that activin E has several functions: initially, it is needed to induce thermogenesis by stimulating beige adipocytes in WAT; then, its overexpression raises thermogenesis and insulin sensitivity by stimulating activity of brown adipocytes in BAT; finally, activin E is closely related to FGF21 in WAT, which may increase its expression in brown pre-adipocyte culture.”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [68]
Activin E may be a therapeutic target for obesity.
“It is inferred that activin E may be a therapeutic target for obesity [68].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [68]
In mice, overexpression of activin E raises thermogenesis and insulin sensitivity by stimulating brown adipocytes in BAT.
“A study in mice showed that activin E has several functions: initially, it is needed to induce thermogenesis by stimulating beige adipocytes in WAT; then, its overexpression raises thermogenesis and insulin sensitivity by stimulating activity of brown adipocytes in BAT; finally, activin E is closely related to FGF21 in WAT, which may increase its expression in brown pre-adipocyte culture.”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [68]
Circulating levels of activin-E are elevated in high-fat diet-fed mice and are thought to contribute to resistance to body weight gain.
“Furthermore, circulating levels of activin-E are elevated in high-fat diet-fed mice and are thought to contribute to resistance to body weight gain [28,30].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [30]
Activin-E directly enhances the expression of uncoupling protein 1 (UCP1) and fibroblast growth factor (FGF21) in cultured brown pre-adipocytes.
“activin-E directly enhances the expression of uncoupling protein 1 (UCP1) and fibroblast growth factor (FGF21), two important regulators of adipose thermogenesis, in cultured brown pre-adipocytes [30].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [30]
Activin-E is an important regulator of energy expenditure and insulin sensitivity in rodents.
“and was recently identified as an important regulator of energy expenditure and insulin sensitivity in rodents [30]”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [30]
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References 39 · Cited by 77
- Authors
- Hashimoto, O., Funaba, M., Sekiyama, K., Doi, S., Shindo, D., Satoh, R., Itoi, H., Oiwa, H., Morita, M., Suzuki, C., Sugiyama, M., Yamakawa, N., Takada, H., Matsumura, S., Inoue, K., Oyadomari, S., Sugino, H., & Kurisaki, A.
- Affiliations
- Kitasato University (JP)
- Kyoto University (JP)
- National Institute of Advanced Industrial Science and Technology (JP)
- Tokushima University (JP)
- Corresponding author
- Hashimoto, Osamu
- Funaba, Masayuki
- Kurisaki, Akira
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 25
- Issue
- 5
- Pages
- 1193-1203
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2899245278
- Cited by
- 77
- References
- 39
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 9 · 2023: 12 · 2022: 17 · 2021: 13 · 2020: 4 · 2019: 9
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (publishedVersion, cc-by)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
- Funders
- The Japan Society for the Promotion of Science (JP21580370)
- JSPS (JP2, 6450442, 5640109)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- hepatokines, energy homeostasis, brown adipose tissue, white adipose tissue, thermogenesis, cold exposure, UCP1, FGF21, insulin sensitivity, obesity, TGF-beta signaling, activin type I receptor
- MeSH terms
- Adipocytes, Beige, Animals, Body Weight, Adipose Tissue, Brown, Cell Differentiation, Cold Temperature, Energy Metabolism, Fibroblast Growth Factors, Glucose, Homeostasis, Humans, Insulin Resistance, Liver, Male, Mice, Inbred C57BL, Transforming Growth Factor beta, Mice, Knockout, Thermogenesis, Inhibin-beta Subunits, Activins, Activin Receptors, Type I, Lipid Metabolism, Adipose Tissue, White, Adipocytes, Brown, HEK293 Cells
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