Hepatokine Fetuin B expression is regulated by leptin-STAT3 signalling and associated with leptin in obesity.

Abstract

Obesity is an expanding global public health problem and a leading cause of metabolic disorders. The hepatokine Fetuin B participates in regulating insulin resistance, glucose metabolism and liver steatosis. However, the mechanism underlying Fetuin B activation remains unclear. Our previous population-based study demonstrated a significant association between serum Fetuin B and body fat mass in an obese population, which indicates its potential in mediating obesity-related metabolic disorders. In the present study, we further revealed a significant correlation between Fetuin B and leptin, the classic adipokine released by expanding adipose tissue, in this obese population. Consistently, elevated Fetuin B and leptin levels were confirmed in diet-induced obese mice. Furthermore, an in vitro study demonstrated that the leptin signalling pathway directly activated the transcription and expression of Fetuin B in primary hepatocytes and AML12 cells in a STAT3-dependent manner. STAT3 binds to the response elements on FetuB promoter to directly activate FetuB transcription. Finally, the mediating effect of Fetuin B in insulin resistance induced by leptin was confirmed according to mediation analysis in this obese population. Therefore, our study identifies leptin-STAT3 as an upstream signalling pathway that activates Fetuin B and provides new insights into the pathogenic mechanisms of obesity-related metabolic disorders.

• Authors: Dongmei Wang, Menghua Wu, Xiaofang Zhang, Long Li, Mingzhu Lin, Xiulin Shi, Yan Zhao, Caoxin Huang, Xuejun Li
• Journal: Scientific reports (Sci Rep) Vol. 12 Issue 1 Pg. 12869 (07 27 2022) ISSN: 2045-2322 [Electronic] England
• PMID: 35896788 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• FETUB protein, human
• Fetuin-B
• LEP protein, human
• Leptin
• STAT3 Transcription Factor
• STAT3 protein, human

Topics

• Animals
• Fatty Liver (complications)
• Fetuin-B (genetics)
• Humans
• Insulin Resistance
• Leptin (metabolism)
• Mice
• Obesity (metabolism)
• STAT3 Transcription Factor (metabolism)