Inhibin βE (INHBE) is a possible insulin resistance-associated hepatokine identified by comprehensive gene expression analysis in human liver biopsy samples
Open accessAbstract
The liver plays a major role in whole-body energy homeostasis by releasing secretory factors, termed hepatokines. To identify novel target genes associated with insulin resistance, we performed a comprehensive analysis of gene expression profiles using a DNA chip method in liver biopsy samples from humans with varying degrees of insulin resistance. Inhibin βE (INHBE) was identified as a novel putative hepatokine with hepatic gene expression that positively correlated with insulin resistance and body mass index in humans. Quantitative real time-PCR analysis also showed an increase in INHBE gene expression in independent liver samples from insulin-resistant human subjects. Additionally, Inhbe gene expression increased in the livers of db/db mice, a rodent model of type 2 diabetes. To preliminarily screen the role of Inhbe in vivo in whole-body energy metabolic status, hepatic mRNA was knocked down with siRNA for Inhbe (siINHBE) in db/db mice. Treatment with siINHBE suppressed body weight gain during the two-week experimental period, which was attributable to diminished fat rather than lean mass. Additionally, treatment with siINHBE decreased the respiratory quotient and increased plasma total ketone bodies compared with treatment with non-targeting siRNA, both of which suggest enhanced whole-body fat utilization. Our study suggests that INHBE functions as a possible hepatokine to alter the whole-body metabolic status under obese insulin-resistant conditions.
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Activin-E levels in humans are increased in individuals with obesity and insulin resistance.
“Supporting a potential role for activin-E in human diseases, activin-E levels in humans are increased in individuals with obesity and insulin resistance [31].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [31]
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- Authors
- Sugiyama, M., Kikuchi, A., Misu, H., Igawa, H., Ashihara, M., Kushima, Y., Honda, K., Suzuki, Y., Kawabe, Y., Kaneko, S., & Takamura, T.
- Affiliations
- Chugai Pharmaceutical Co., Ltd. (Japan) (JP)
- Kanazawa University (JP)
- Corresponding author
- Kikuchi, Akihiro
- Takamura, Toshinari
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-03-29
- Volume
- 13
- Issue
- 3
- Pages
- e0194798
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5875797
- OpenAlex
- W2794620918
- Cited by
- 52
- References
- 37
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 2 · 2019: 4 · 2018: 2
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Kanazawa University
- Chugai Pharmaceutical
- Japan Society for the Promotion of Science (17H04199, 16K09740, 17K09822)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- hepatokines, insulin resistance, type 2 diabetes, obesity, hepatic gene expression, db/db mice, siRNA knockdown, weight gain, fat utilization, ketone bodies, respiratory quotient, energy metabolism
- MeSH terms
- Adipose Tissue, Animals, Biopsy, Body Weight, Female, Humans, Insulin Resistance, Liver, Male, Middle Aged, Phenotype, RNA, Messenger, Gene Expression Profiling, Inhibin-beta Subunits, RNA, Small Interfering, Mice
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