Loss of autophagy impairs physiological steatosis by accumulation of NCoR1.

Life science alliance 2020 Jan

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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. © 2019 Takahashi et al.

Citation

Shun-Saku Takahashi, Yu-Shin Sou, Tetsuya Saito, Akiko Kuma, Takayuki Yabe, Yuki Sugiura, Hyeon-Cheol Lee, Makoto Suematsu, Takehiko Yokomizo, Masato Koike, Shuji Terai, Noboru Mizushima, Satoshi Waguri, Masaaki Komatsu. Loss of autophagy impairs physiological steatosis by accumulation of NCoR1. Life science alliance. 2020 Jan;3(1)