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Hepatokine Fetuin B expression is regulated by leptin-STAT3 signalling and associated with leptin in obesity
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Hepatokine Fetuin B expression is regulated by leptin-STAT3 signalling and associated with leptin in obesity
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Journal Article
Hepatokine Fetuin B expression is regulated by leptin-STAT3 signalling and associated with leptin in obesity
2022
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
