PGC1α protects against hepatic steatosis and insulin resistance via enhancing IL10-mediated anti-inflammatory response
| Autor: | Ye Feng, Li Chen, Daojun Diao, Weiyan Shen, Zhenyu Ju, Lingling Zhang, Tangliang Li, Xudong Zhu, Chaohui Yu, Peihao Liu, Leiming Liu, Hu Wang, Fan Yang, Weihua Zhou, Xingyong Wan, Jian Ren, Qi Zhao, Jing Li, Sheng Yan |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Anti-Inflammatory Agents Alpha (ethology) Gene Expression Inflammation Protective Agents Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Insulin resistance Internal medicine Genetics Medicine Animals Neutralizing antibody Molecular Biology biology business.industry Fatty liver Lipid metabolism medicine.disease Lipid Metabolism Antibodies Neutralizing Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Interleukin-10 Mitochondria Fatty Liver Interleukin 10 030104 developmental biology Endocrinology Liver biology.protein Hepatocytes Steatosis medicine.symptom Insulin Resistance business 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(8) |
| ISSN: | 1530-6860 |
| Popis: | Inflammatory responses are pivotal incidences in hepatic metabolic derangements. However, the underlying mechanism remains elusive. The present study aimed to evaluate the role of peroxisome proliferator-activated receptor-gamma, coactivator 1 alpha (PGC1α) in IL10-mediated anti-inflammatory response, and its role in hepatic steatosis and insulin resistance. Hepatocyte-specific PGC1α knock-in (LivPGC1α) mice and the control mice were fed high-fat diet (HFD) for 8 weeks. IL-10 neutralizing antibody was injected into the liver of PGC1α mice. A variety of biological and histological approaches were applied to assess hepatic function. We demonstrated that hepatic PGC1α expression was significantly reduced in mice fed HFD. LivPGC1α livers exhibited enhanced gene expressions involving mitochondrial function, and favored an accelerated lipid metabolism upon HFD. Meanwhile, LivPGC1α mice revealed improved hepatic steatosis and insulin resistance. Mechanistically, PGC1α bound and activated the promotor region of IL-10, thereby attenuating inflammatory response in the liver. Administration of IL10 neutralizing antibody to LivPGC1α mice abolished PGC1α-mediated anti-inflammatory effects in mice. Further, IL-10 neutralizing antibody intervention aggravated hepatic steatosis and insulin resistance in LivPGC1α mice. Taken together, our data indicated that hepatic-specific overexpression of PGC1α exerts a beneficial role in the regulation of hepatic steatosis and insulin resistance via enhancing IL10-mediated anti-inflammatory response. Pharmacological activation of PGC1α-IL10 axis may be promising for the treatment of fatty liver diseases. |
| Databáze: | OpenAIRE |
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