Inhibin βE (INHBE) is a possible insulin resistance-associated hepatokine identified by comprehensive gene expression analysis in human liver biopsy samples

• Published in: PloS one Vol. 13; no. 3; p. e0194798
• Main Authors: Sugiyama, Masakazu, Kikuchi, Akihiro, Misu, Hirofumi, Igawa, Hirobumi, Ashihara, Motooki, Kushima, Youichi, Honda, Kiyofumi, Suzuki, Yoshiyuki, Kawabe, Yoshiki, Kaneko, Shuichi, Takamura, Toshinari
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.03.2018; Public Library of Science (PLoS)
• Subjects: Biology; Biology and life sciences; Biopsy; Body fat; Body mass; Body mass index; Body size; Body weight; Body weight gain; Deoxyribonucleic acid; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); DNA; Endocrinology; Energy balance; Gene expression; Glucose; Growth factors; Growth hormones; Homeostasis; Hormone replacement therapy; Human subjects; Inhibin; Insulin; Insulin resistance; Ketones; Liver; Medicine and Health Sciences; Metabolism; Mice; Musculoskeletal system; Mutation; Obesity; Pharmaceuticals; Research and Analysis Methods; Respiratory quotient; Rodents; siRNA; Target recognition; University graduates; United States > US; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0194798

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.