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

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 populati...

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Bibliographic Details
Published in:Scientific reports 2022-07, Vol.12 (1), p.12869-12869, Article 12869
Main Authors: Wang, Dongmei, Wu, Menghua, Zhang, Xiaofang, Li, Long, Lin, Mingzhu, Shi, Xiulin, Zhao, Yan, Huang, Caoxin, Li, Xuejun
Format: Article
Language:English
Subjects:
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692/699/317
Adipose tissue
Body fat
Fatty liver
Glucose metabolism
Hepatocytes
Humanities and Social Sciences
Insulin
Insulin resistance
Leptin
Metabolic disorders
multidisciplinary
Obesity
Population
Population studies
Public health
Regulatory sequences
Science
Science (multidisciplinary)
Signal transduction
Stat3 protein
Steatosis
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-17000-w