RT Journal Article
SR Electronic
T1 Loss of autophagy impairs physiological steatosis by accumulation of NCoR1
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900513
DO 10.26508/lsa.201900513
VO 3
IS 1
A1 Takahashi, Shun-saku
A1 Sou, Yu-Shin
A1 Saito, Tetsuya
A1 Kuma, Akiko
A1 Yabe, Takayuki
A1 Sugiura, Yuki
A1 Lee, Hyeon-Cheol
A1 Suematsu, Makoto
A1 Yokomizo, Takehiko
A1 Koike, Masato
A1 Terai, Shuji
A1 Mizushima, Noboru
A1 Waguri, Satoshi
A1 Komatsu, Masaaki
YR 2020
UL https://www.life-science-alliance.org/content/3/1/e201900513.abstract
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.