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- Title
Adiponectin Alleviates Diet-Induced Inflammation in the Liver by Suppressing MCP-1 Expression and Macrophage Infiltration.
- Authors
Ryu, Jiyoon; Hadley, Jason T.; Li, Zhi; Dong, Feng; Xu, Huan; Xin, Xiaoban; Zhang, Ye; Chen, Cang; Li, Senlin; Guo, Xiaoning; Zhao, Jared L.; Leach, Robin J.; Abdul-Ghani, Muhammad A.; DeFronzo, Ralph A.; Kamat, Amrita; Liu, Feng; Dong, Lily Q.
- Abstract
Adiponectin is an adipokine that exerts insulin-sensitizing and anti-inflammatory roles in insulin target tissues including liver. While the insulin-sensitizing function of adiponectin has been extensively investigated, the precise mechanism by which adiponectin alleviates diet-induced hepatic inflammation remains elusive. Here, we report that hepatocyte-specific knockout (KO) of the adaptor protein APPL2 enhanced adiponectin sensitivity and prevented mice from developing high-fat diet-induced inflammation, insulin resistance, and glucose intolerance, although it caused fatty liver. The improved anti-inflammatory and insulin-sensitizing effects in the APPL2 hepatocyte-specific KO mice were largely reversed by knocking out adiponectin. Mechanistically, hepatocyte APPL2 deficiency enhances adiponectin signaling in the liver, which blocks TNF-α-stimulated MCP-1 expression via inhibiting the mTORC1 signaling pathway, leading to reduced macrophage infiltration and thus reduced inflammation in the liver. With results taken together, our study uncovers a mechanism underlying the anti-inflammatory role of adiponectin in the liver and reveals the hepatic APPL2-mTORC1-MCP-1 axis as a potential target for treating overnutrition-induced inflammation in the liver.
- Subjects
HEPATITIS; ADIPONECTIN; MACROPHAGES; ADAPTOR proteins; GLUCOSE intolerance; BIOCHEMISTRY; RESEARCH; INFLAMMATION; LIVER; FATTY liver; ANIMAL experimentation; RESEARCH methodology; ANIMAL nutrition; MEDICAL cooperation; EVALUATION research; CELL motility; PHENOMENOLOGY; COMPARATIVE studies; INFLAMMATORY mediators; EPITHELIAL cells; CARRIER proteins; INSULIN resistance; MICE
- Publication
Diabetes, 2021, Vol 70, Issue 6, p1303
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db20-1073