Inhibin βE (INHBE) is a possible insulin resistance-associated hepatokine identified by comprehensive gene expression analysis in human liver biopsy samples
| Autor: | Kiyofumi Honda, Hirobumi Igawa, Hirofumi Misu, Motooki Ashihara, Yoshiyuki Suzuki, Akihiro Kikuchi, Yoshiki Kawabe, Toshinari Takamura, Youichi Kushima, Shuichi Kaneko, Masakazu Sugiyama |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Physiology medicine.medical_treatment Biopsy Adipose tissue lcsh:Medicine Type 2 diabetes Biochemistry Fats Mice 0302 clinical medicine Endocrinology Gene expression Medicine and Health Sciences Insulin Small interfering RNAs RNA Small Interfering lcsh:Science Inhibin-beta Subunits Multidisciplinary medicine.diagnostic_test Animal Models Middle Aged Lipids Nucleic acids Phenotype Adipose Tissue Liver Experimental Organism Systems Physiological Parameters Liver biopsy Ketone bodies Female Anatomy Research Article medicine.medical_specialty 030209 endocrinology & metabolism Mouse Models Biology Research and Analysis Methods INHBE Gene 03 medical and health sciences Insulin resistance Model Organisms Internal medicine medicine Genetics Animals Humans RNA Messenger Obesity Non-coding RNA Diabetic Endocrinology Biology and life sciences Endocrine Physiology Gene Expression Profiling lcsh:R Body Weight medicine.disease Hormones Gene regulation 030104 developmental biology Biological Tissue RNA lcsh:Q Insulin Resistance |
| Zdroj: | PLoS ONE PLoS ONE, Vol 13, Iss 3, p e0194798 (2018) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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