Coffee enhances the expression of chaperones and antioxidant proteins in rats with nonalcoholic fatty liver disease

Transl Res. 2014 Jun;163(6):593-602. doi: 10.1016/j.trsl.2013.12.001. Epub 2013 Dec 4.

Abstract

Coffee consumption is inversely related to the degree of liver injury in patients with nonalcoholic fatty liver disease (NAFLD). Molecular mediators contributing to coffee's beneficial effects in NAFLD remain to be elucidated. In this study, we administrated decaffeinated espresso coffee or vehicle to rats fed an high-fat diet (HFD) for 12 weeks and examined the effects of coffee on liver injury by using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) proteomic analysis combined with mass spectrometry. Rats fed an HFD and water developed panacinar steatosis, lobular inflammation, and mild fibrosis, whereas rats fed an HFD and coffee exhibited only mild steatosis. Coffee consumption increased liver expression of the endoplasmic reticulum chaperones glucose-related protein 78 and protein disulfide-isomerase A3; similarly, coffee drinking enhanced the expression of the mitochondrial chaperones heat stress protein 70 and DJ-1. Furthermore, in agreement with reduced hepatic levels of 8-isoprostanes and 8-hydroxy-2'-deoxyguanosine, proteomic analysis showed that coffee consumption induces the expression of master regulators of redox status (i.e., peroxiredoxin 1, glutathione S-transferase α2, and D-dopachrome tautomerase). Last, proteomics revealed an association of coffee intake with decreased expression of electron transfer flavoprotein subunit α, a component of the mitochondrial respiratory chain, involved in de novo lipogenesis. In this study, we were able to identify by proteomic analysis the stress proteins mediating the antioxidant effects of coffee; moreover, we establish for the first time the contribution of specific coffee-induced endoplasmic reticulum and mitochondrial chaperones ensuring correct protein folding and degradation in the liver.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Coffee*
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Electrophoresis, Gel, Two-Dimensional
  • Endoplasmic Reticulum / metabolism
  • Fatty Liver / diet therapy*
  • Fatty Liver / genetics
  • Fatty Liver / metabolism*
  • Gene Expression
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / biosynthesis
  • Heat-Shock Proteins / genetics
  • Male
  • Mitochondria, Liver / metabolism
  • Molecular Chaperones / metabolism*
  • Non-alcoholic Fatty Liver Disease
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism
  • Proteomics
  • Rats
  • Rats, Wistar
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tandem Mass Spectrometry
  • Translational Research, Biomedical

Substances

  • Antioxidants
  • Coffee
  • GRP78 protein, rat
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Molecular Chaperones
  • PDIA3 protein, rat
  • Protein Disulfide-Isomerases