1. Academic Validation
  2. Adiponectin Alleviates Diet-Induced Inflammation in the Liver by Suppressing MCP-1 Expression and Macrophage Infiltration

Adiponectin Alleviates Diet-Induced Inflammation in the Liver by Suppressing MCP-1 Expression and Macrophage Infiltration

  • Diabetes. 2021 Jun;70(6):1303-1316. doi: 10.2337/db20-1073.
Jiyoon Ryu 1 Jason T Hadley 1 Zhi Li 1 Feng Dong 2 Huan Xu 1 Xiaoban Xin 1 Ye Zhang 1 Cang Chen 2 Senlin Li 2 3 Xiaoning Guo 1 Jared L Zhao 1 Robin J Leach 1 Muhammad A Abdul-Ghani 2 Ralph A DeFronzo 2 Amrita Kamat 2 4 Feng Liu 3 Lily Q Dong 5
Affiliations

Affiliations

  • 1 Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX.
  • 2 Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX.
  • 3 Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX.
  • 4 Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX.
  • 5 Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX dongq@uthscsa.edu.
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.

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