한빛사논문
- 조회362
Thuy T P Nguyen1, Do-Young Kim2, Seung-Soon Im2*, Tae-Il Jeon1*
1Department of Animal Science, Chonnam National University, Gwangju, Republic of Korea.
2Department of Physiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
*Corresponding author.
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the global population. However, its pathogenesis is not completely understood. In our recent study, we have demonstrated that in a high-fat diet-induced liver steatosis model, the activation of SREBF1/SREBP-1c (sterol regulatory element binding transcription factor 1) directly upregulates Mir216a transcription, which inhibits CTH/CSE (cystathionase (cystathionine gamma-lyase)) expression and its function in hydrogen sulfide (H2S) production. Reduced H2S production suppresses the sulfhydration of ULK1 (unc-51 like autophagy activating kinase 1), consequently inhibiting autophagic flux and lipid droplet turnover. A single substitution mutation (C951S) in ULK1 or the silencing of CTH impairs ULK1 sulfhydration-mediated lipophagy, thereby promoting hepatic steatosis in mice. Interestingly, the sulfhydration of ULK1 increases its intrinsic kinase activity to modulate autophagy at both initiation and progression stages of autophagic catabolic flux. This study reveals that SREBF1/SREBP-1c contributes to hepatic lipid accumulation through its combined effect of increased lipid synthesis coupled with decreased lipid degradation mediated by autophagic dysregulation.
논문정보
- Article commentary
- 2021년 08월 (BRIC 등록일 2021-09-03)
- 국내 연구진
- 생명과학 > 분자생물학
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