PT  - JOURNAL ARTICLE
AU  - Takahashi, Shun-saku
AU  - Sou, Yu-Shin
AU  - Saito, Tetsuya
AU  - Kuma, Akiko
AU  - Yabe, Takayuki
AU  - Sugiura, Yuki
AU  - Lee, Hyeon-Cheol
AU  - Suematsu, Makoto
AU  - Yokomizo, Takehiko
AU  - Koike, Masato
AU  - Terai, Shuji
AU  - Mizushima, Noboru
AU  - Waguri, Satoshi
AU  - Komatsu, Masaaki
TI  - Loss of autophagy impairs physiological steatosis by accumulation of NCoR1
AID  - 10.26508/lsa.201900513
DP  - 2020 Jan 01
TA  - Life Science Alliance
PG  - e201900513
VI  - 3
IP  - 1
4099  - https://www.life-science-alliance.org/content/3/1/e201900513.short
4100  - https://www.life-science-alliance.org/content/3/1/e201900513.full
SO  - Life Sci. Alliance2020 Jan 01; 3
AB  - 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.