TY - JOUR T1 - Loss of autophagy impairs physiological steatosis by accumulation of NCoR1 JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900513 VL - 3 IS - 1 SP - e201900513 AU - Shun-saku Takahashi AU - Yu-Shin Sou AU - Tetsuya Saito AU - Akiko Kuma AU - Takayuki Yabe AU - Yuki Sugiura AU - Hyeon-Cheol Lee AU - Makoto Suematsu AU - Takehiko Yokomizo AU - Masato Koike AU - Shuji Terai AU - Noboru Mizushima AU - Satoshi Waguri AU - Masaaki Komatsu Y1 - 2020/01/01 UR - https://www.life-science-alliance.org/content/3/1/e201900513.abstract N2 - 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. ER -