Oleanolic Acid Inhibits SCD1 Gene Expression to Ameliorate Fructose-Induced Hepatosteatosis through SREBP1c-Dependent and -Independent Mechanisms

作者全名："Yao, Ling; Wang, Meng; Zhang, Jun; Luo, Xianqin; Yuan, Chunlin; Bai, Ruojun; Wang, Tongzhuang; Xi, Yumeng; Li, Chunli; Ke, Dazhi; Yamahara, Johji; Li, Yuhao; Yi, Yongfen; Wang, Shang; Wang, Jianwei"

作者地址："[Yao, Ling; Wang, Meng; Zhang, Jun; Luo, Xianqin; Yuan, Chunlin; Bai, Ruojun; Wang, Tongzhuang; Xi, Yumeng; Wang, Shang; Wang, Jianwei] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Yao, Ling; Yi, Yongfen] Chongqing Med Univ, Dept Pathol Mol Med, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Yao, Ling; Yi, Yongfen] Chongqing Med Univ, Basic Med Coll, Canc Res Ctr, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Li, Chunli] Chongqing Med Univ, Inst Life Sci, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Ke, Dazhi] Chongqing Med Univ, Affiliated Hosp 2, 74 Linjiang Rd, Chongqing 400010, Peoples R China; [Yamahara, Johji] Pharmafood Inst, Kyoto 6028136, Japan; [Li, Yuhao] Sydney Inst Hlth Sci, Sydney Inst Tradit Chinese Med, Endocrinol & Metab Grp, Sydney, NSW 2000, Australia"

通信作者："Wang, S; Wang, JW (通讯作者)，Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：MOLECULAR NUTRITION & FOOD RESEARCH

ESI学科分类：AGRICULTURAL SCIENCES

WOS号：WOS:000982430900001

JCR分区：Q1

影响因子：4.5

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：hepatosteatosis; oleanolic acid; oleic acid; SCD1; SREBP1c

摘要："ScopeThe mechanisms of oleanolic acid (OA) regulating hepatic sterol regulatory element-binding protein (SREBP) 1c/stearoyl-CoA desaturase (SCD) 1 pathway to ameliorate fructose-induced hepatosteatosis are investigated. Methods and resultsRats treated with 10% w/v fructose solution are co-administered by OA for 5 weeks, and then sacrifice after fasting for 14 h. OA reverses the fructose-induced increase in hepatic triglyceride (TG) content and downregulates Scd1 mRNA expression. However, two upstream transcription factors, ChREBP and SREBP1c, remain at normal levels with or without fructose and/or OA. In vivo and in vitro studies using SREBP1c(-/-) mice and HepG2 cell models show that OA also inhibits SCD1 gene overexpression and high hepatic TG levels induced by fructose. On the other hand, in SCD1(-/-) mice, when the fructose diet is supplemented with high levels of oleic acid (OLA) to compensate for the deficiency of SCD1, OA inhibits hepatic SREBP1c and lipogenic gene expression and reduces hepatic OLA (C18:1) production to improve fructose and/or OLA induced liver lipid deposition. Furthermore, OA promotes PPAR alpha and AMPK to enhance fatty acid oxidation in fructose + OLA-fed SCD1(-/-) mice. ConclusionOA may inhibit SCD1 gene expression to ameliorate fructose-induced hepatosteatosis through SREBP1c-dependent and -independent mechanisms."

基金机构："Chongqing Health Commission [ZY201702133]; Chongqing Education Committee [KJQN201800432]; Chongqing Science and Technology Bureau [cstc2017jcyjAX0374, cstc2020jcyj-msxmX0466, CSTB2022NSCQ-MSX1478]; Chongqing Yuzhong Science and Technology Commission [20190117]"

基金资助正文："Acknowledgements This work was financially supported by Chongqing Health Commission (grant no. ZY201702133), Chongqing Education Committee (grant no. KJQN201800432), the Chongqing Science and Technology Bureau (grant no. cstc2017jcyjAX0374, cstc2020jcyj-msxmX0466 and CSTB2022NSCQ-MSX1478) and the Chongqing Yuzhong Science and Technology Commission (grant no. 20190117)."