2. Academic Validation
  3. Quercetin ameliorates HFD-induced NAFLD by promoting hepatic VLDL assembly and lipophagy via the IRE1a/XBP1s pathway

Quercetin ameliorates HFD-induced NAFLD by promoting hepatic VLDL assembly and lipophagy via the IRE1a/XBP1s pathway

  • Food Chem Toxicol. 2018 Apr;114:52-60. doi: 10.1016/j.fct.2018.02.019.
Xinhong Zhu 1,  Ting Xiong 1,  Peiyi Liu 1,  Xiaoping Guo 1,  Lin Xiao 1,  Feng Zhou 1,  Yuhan Tang 2,  Ping Yao 3
Affiliations

Affiliations

  • 1 Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 2 Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: [email protected].
  • 3 Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: [email protected].
PMID: 29438776 DOI: 10.1016/j.fct.2018.02.019
Abstract

The consumption of a quercetin-rich diet has been well-established as a feasible method against non-alcoholic fatty liver disease (NAFLD); however, the molecular mechanisms underlying the progression of NAFLD and its intervention by quercetin remain largely obscure. Male Sprague-Dawley rats fed high-fat diet (HFD), and HepG2 cells stimulated with free fatty acid, were treated with quercetin and various pharmacological reagents to explore the effect of signaling pathways involved in endoplasmic reticulum stress on very low-density lipoprotein (VLDL) assembly and lipophagy. Quercetin intake decreased hepatic TG content by 39%, with a 1.5-fold increase in VLDL, and up-regulated spliced X-box binding protein 1 (XBP1s) expression compared with the HFD group. Thapsigargin or STF-083010 (an IRE1α endonuclease inhibitor) decreased VLDL content in a dose-dependent manner, partially counteracting the protective effects of quercetin, 4-PBA or APY-29 (an IRE1α endonuclease activator). Additionally, microsomal TG-transfer protein complex expression was increased with quercetin-treated and down-regulated by STF-083010. Moreover, quercetin increased co-localization of lysosomes with lipid droplets (LDs) accompanied by decreased p62 accumulation. STF-083010 partially abolished the effect of quercetin on LDs Autophagy in an mTOR-independent manner. Collectively, these findings demonstrate that hepatic VLDL assembly and lipophagy are the main targets of quercetin against NAFLD via the IRE1a/XBP1s pathway.

Keywords

Inositol-requiring transmembrane kinase/endoribonuclease 1α; Lipophagy; NAFLD; Quercetin; Spliced X-box binding protein 1; Very low-density lipoprotein.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-17537
    99.90%, IRE1 Inhibitor