Aberrant elevation of FTO levels promotes liver steatosis by decreasing the m^(6)A methylation and increasing the stability of SREBF1 and ChREBP mRNAs
作者机构：CAS Key Laboratory of NutritionMetabolism and Food SafetyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of Sciencesand Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai 200031China Innovation Center for Intervention of Chronic Disease and Promotion of HealthShanghai 200031China Department of Endocrinology and MetabolismZhongshan HospitalFudan UniversityShanghai 200031China State Key Laboratory of Food Science and TechnologySchool of Food Science and TechnologyJiangnan UniversityWuxi 214122China Shanghai Diabetes InstituteShanghai Key Laboratoryof Diabetes MelitusShanghai Clinical Centre for DiabetesShanghai jiao Tong University Affiliated Sixth People's HospitalShanghai 200233China Key Laboratory of Food Safety Risk AssessmentMinistry of HealthBeijing 100021China
出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)
年 卷 期：2022年第14卷第9期
页 面：40-53页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：This work was supported by the Chinese Ministry of Science and Technology(2021YFA1100500) the National Natural Science Foundation of China(NSFC,91957205,82070821,and 82000805) Youth Innovation Promotion Association,Chinese Academy of Sciences(2021261) Pujiang Talent Program from the Science and Technology Commission of Shanghai Municipality(21PJ1416100) Young Elite Scientists Sponsorship Program by China Association for Science and Technology(2020QNRC001) the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province,Jiangnan University(2022-3-1) NHC Key Laboratory of Food Safety Risk Assessment(2020K02)
主 题：FTO m^(6)A SREBF1 ChREBP lipogenesis NAFLD
摘 要：Previous studies have indicated an association of fat mass and obesity-associated(FTO)with nonalcoholic fatty liver disease(NAFLD),the most common chronic liver disease *** study aimed to decipher the complex role of FTO in hepatic lipid *** found that a decrease in N^(6)-methyladenosine(m^(6)A)RNA methylation in the liver of mice fed with a high-fat diet(HFD)was accompanied by an increase in FTO *** of FTO in the liver promoted triglyceride accumulation by upregulating the expression of lipogenic *** studies revealed that FTO could stabilize the mRNAs of sterol regulatory element binding transcription factor 1(SREBF1)and carbohydrate responsive element binding protein(ChREBP),two master lipogenic transcription factors,by demethylating m^(6)A *** ofeither SREBF1 or ChREBP attenuated the lipogenic effect of FTO,suggesting that they are bona fide effectors for FTO in regulating *** could stimulate FTO transcription through a mechanism involving the action of intranuclear insulin receptor beta,while knockdown of FTO abrogated the lipogenic effect of *** ofFTo by entacapone decreased the expression of SREBF1,ChREBP,and downstream lipogenic genes,ameliorating liver steatosis in HFD-fed ***,our study established a critical role of FTO in both the insulin-regulated hepatic lipogenesis and the pathogenesis of NAFLD and provided a potential strategyfor treating NAFLD.
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