Loss of autophagy impairs physiological steatosis by accumulation of NCoR1
| Autor: | Akiko Kuma, Masato Koike, Shuji Terai, Makoto Suematsu, Shun saku Takahashi, Takayuki Yabe, Tetsuya Saito, Satoshi Waguri, Yu-shin Sou, Masaaki Komatsu, Takehiko Yokomizo, Noboru Mizushima, Yuki Sugiura, Hyeon-Cheol Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis Plant Science Transfection Biochemistry Genetics and Molecular Biology (miscellaneous) Autophagy-Related Protein 7 03 medical and health sciences Transactivation Gene Knockout Techniques Mice 0302 clinical medicine Lipid droplet medicine Autophagy Animals Humans Nuclear Receptor Co-Repressor 1 Liver X receptor Nuclear receptor co-repressor 1 Research Articles Triglycerides Liver X Receptors Mice Knockout Ecology Chemistry Lipogenesis Fatty Acids Fasting Hep G2 Cells Lipid Droplets medicine.disease Cell biology Fatty Liver Mice Inbred C57BL 030104 developmental biology Lipotoxicity Nuclear receptor 030220 oncology & carcinogenesis Steatosis Research Article |
| Zdroj: | Life Science Alliance |
| ISSN: | 2575-1077 |
| Popis: | Autophagy regulates fatty acid and triglyceride synthesis at the transcriptional level by fine-tuning the levels of NCoR1, a negative regulator of nuclear receptors. Defective autophagy impairs physiological steatosis both under fasting conditions and after hepatectomy. Lipid droplets (LDs) are dynamic organelles that store neutral lipids during times of energy excess, such as after a meal. LDs serve as an energy reservoir during fasting and have a buffering capacity that prevents lipotoxicity. Autophagy and the autophagic machinery have been proposed to play a role in LD biogenesis, but the underlying molecular mechanism remains unclear. Here, we show that when nuclear receptor co-repressor 1 (NCoR1), which inhibits the transactivation of nuclear receptors, accumulates because of autophagy suppression, LDs decrease in size and number. Ablation of ATG7, a gene essential for autophagy, suppressed the expression of gene targets of liver X receptor α, a nuclear receptor responsible for fatty acid and triglyceride synthesis in an NCoR1-dependent manner. LD accumulation in response to fasting and after hepatectomy was hampered by the suppression of autophagy. These results suggest that autophagy controls physiological hepatosteatosis by fine-tuning NCoR1 protein levels. |
| Databáze: | OpenAIRE |
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