White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice
| Autor: | Tetsuo Takehara, Tomohide Tatsumi, Ryotaro Sakamori, Kumiko Shirai, Sadatsugu Sakane, Yuki Makino, Kenji Fukumoto, Takahiro Kodama, Yuta Myojin, Hayato Hikita, Youichi Sasaki, Ryoko Yamada, Yuki Tahata, Naoki Mizutani, Shinnosuke Kudo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
eWAT
epididymal white adipose tissue HFD high-fat diet medicine.medical_specialty Adipose tissue Nonalcoholic Steatohepatitis Inflammation mTOR mammalian target of rapamycin RC799-869 White adipose tissue iWAT inguinal white adipose tissue PCR polymerase chain reaction Non-alcoholic Fatty Liver Disease Fibrosis ALT alanine aminotransferase 4-HNE 4-hydroxynonenal Internal medicine Lipid droplet Nonalcoholic fatty liver disease Autophagy medicine Humans Original Research TNF tumor necrosis factor KO knockout Hepatology ND normal diet business.industry Intracellular Signaling Peptides and Proteins Gastroenterology nutritional and metabolic diseases Diseases of the digestive system. Gastroenterology medicine.disease IL interleukin NEFA nonesterified fatty acid Endocrinology Adipose Tissue NAFLD nonalcoholic fatty liver disease FFAs free fatty acids medicine.symptom Steatosis business NASH nonalcoholic steatohepatitis TUNEL deoxyuride-5′-triphosphate biotin nick end labeling |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 5, Pp 1683-1699 (2021) Cellular and Molecular Gastroenterology and Hepatology |
| ISSN: | 2352-345X |
| DOI: | 10.1016/j.jcmgh.2021.07.008 |
| Popis: | Background & Aims Although nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity, the role of adipose tissue in NAFLD is not well-understood. Because autophagy has been reported to be involved in the degradation of lipid droplets, we investigated the role of adipose tissue autophagy in the liver pathogenesis of NAFLD. Methods C57BL/6J mice and adipocyte-specific Atg7-knockout mice (Adipoq-Atg7 KO mice) were fed a high-fat diet (HFD). Results HFD feeding for up to 4 months increased both inguinal and epididymal white adipose tissue (iWAT and eWAT, respectively; the former represents subcutaneous fat, and the latter represents visceral fat) in mice. After HFD feeding, autophagy flux in both types of white adipose tissue was increased, and the levels of Rubicon, a negative autophagy regulator, were decreased, suggesting autophagy promotion. Adipoq-Atg7 KO mice exhibited suppressed autophagy in both iWAT and eWAT. Adipocyte-specific Atg7 KO enhanced HFD-induced iWAT hypertrophy. On the other hand, eWAT levels in Adipoq-Atg7 KO mice were increased after 1 month of HFD feeding but decreased after 4 months of HFD feeding compared with those in wild-type controls. Cleaved caspase 3 and JNK pathway protein expression in eWAT was increased without cytokine elevation in Adipoq-Atg7 KO mice fed an HFD compared with wild-type mice fed an HFD. Adipocyte-specific Atg7 KO decreased serum free fatty acid levels and ameliorated HFD-induced steatosis, liver inflammation, and fibrosis. Conclusions Autophagy was enhanced in the white adipose tissues of mice fed an HFD. Autophagy inhibition in white adipose tissues ameliorated the liver pathology of NAFLD via adipose-liver crosstalk. Graphical abstract |
| Databáze: | OpenAIRE |
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