Diabetes (New York, N.Y.), 2021-06, Vol.70 (6), p.1303-1316
2021
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Details
- Autor(en) / Beteiligte
- Titel
- Adiponectin Alleviates Diet-Induced Inflammation in the Liver by Suppressing MCP-1 Expression and Macrophage Infiltration
- Ist Teil von
- Diabetes (New York, N.Y.), 2021-06, Vol.70 (6), p.1303-1316
- Ort / Verlag
- United States: American Diabetes Association
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0012-1797eISSN: 1939-327XDOI: 10.2337/db20-1073Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8275886
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing - genetics, Adaptor Proteins, Signal Transducing - metabolism, Adaptor Proteins, Signal Transducing - physiology, Adiponectin, Adiponectin - physiology, Animals, Cell Movement - genetics, Chemokine CCL2 - genetics, Chemokine CCL2 - metabolism, Diet, High-Fat - adverse effects, Down-Regulation - genetics, Fatty liver, Fatty Liver - genetics, Fatty Liver - metabolism, Fatty Liver - pathology, Glucose tolerance, Hepatitis - genetics, Hepatitis - immunology, Hepatitis - metabolism, Hepatitis - pathology, Hepatocytes - metabolism, High fat diet, Infiltration, Inflammation, Inflammation - genetics, Inflammation - immunology, Inflammation - metabolism, Inflammation - pathology, Insulin, Insulin resistance, Insulin Resistance - genetics, Intolerance, Liver, Liver - immunology, Liver - metabolism, Liver - pathology, Macrophages, Macrophages - physiology, Male, Mice, Mice, Knockout, Monocyte chemoattractant protein 1, Obesity Studies, Overnutrition, Signal transduction, Tumor necrosis factor-α