Protection by different classes of dietary polyphenols against palmitic acid-induced steatosis, nitro-oxidative stress and endoplasmic reticulum stress in HepG2 hepatocytes. (May 2018)

• Record Type: Journal Article
• Authors: Rafiei, Hossein; Omidian, Kosar; Bandy, Brian
• Is Part Of: Journal of functional foods. Volume 44(2018)
• Page Start: 173
• Page End: 182
• Publication Date: 2018-05
• Subjects: Non-alcoholic fatty liver disease -- Functional food polyphenols -- Endoplasmic reticulum stress -- Oxidative stress -- Mitochondrial dysfunction; AMPK AMP-activated protein kinase -- ATP5G1 ATP synthase, mitochondrial Fo complex, subunit C1 (subunit 9) -- CCCP carbonyl cyanide 3-chlorophenylhydrazone -- CHOP CCAAT-enhancer-binding protein homologous protein -- COX6B1 cytochrome c oxidase subunit VIb polypeptide 1 (ubiquitous) -- EDEM1 ER degradation enhancing alpha-mannosidase like protein 1 -- ER endoplasmic reticulum -- ERdj4 endoplasmic reticulum DnaJ homolog 4 -- GADD34 growth arrest and DNA damage-inducible protein -- GRP78 78 kDa glucose-regulated protein -- iNOS inducible nitric oxide synthase -- MTATP6 mitochondrial DNA-encoded ATP synthase Fo subunit 6 -- MTCO1 mitochondrially encoded cytochrome c oxidase I -- MTCYB mitochondrial DNA-encoded subunit of respiratory Complex III -- MTND1 mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 -- NADH dehydrogenase subunit 1 -- NAFLD non-alcoholic fatty liver disease -- NASH non-alcoholic steatohepatitis -- NDUFS8 NADH dehydrogenase (ubiquinone) Fe-S protein 8 -- NFκB nuclear factor kappa b -- ORP150 150-kDa oxygen-regulated protein -- p-eIF2α phosphorylated eukaryotic translation initiation factor 2 -- PGC1α peroxisome proliferator-activated receptor gamma coactivator 1-alpha -- p-PERK phosphorylated PKR-like ER-resident kinase -- SIRT1 sirtuin 1 -- UPR unfolded protein response -- UQCRC1 ubiquinol-cytochrome c reductase core protein I; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2018.02.033
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Increased load of electron donors (NADH and FADH2 ) originating from fat metabolism to the mitochondrial electron transport chain (ETC) results in increased ROS production due to leakage of electrons from complex I and III. These ROS further cause mitochondrial dysfunction and decrease mitochondrial content. Polyphenols improve the flow of electrons in the ETC possibly by inducing the expression of mitochondrial respiratory complex subunits and improving mitochondrial function leading to protection against the decline in mitochondrial membrane potential. Polyphenols also prevent induction of endoplasmic reticulum chaperones by palmitate, leading to lower expression of pro-apoptotic CHOP . By preventing the decline in ΔΨm and the expression of ER stress chaperones and CHOP, polyphenols may prevent apoptosis involved in the progression of NAFLD. Highlights: Palmitate increased hepatocyte ROS, mitochondrial dysfunction and ER stress. Functional food-relevant polyphenols all prevented steatosis and decreased intracellular ROS. Polyphenols prevented a large increase in iNOS mRNA expression. Some polyphenols helped preserve mitochondrial content and membrane potential. Quercetin most effectively attenuated ER stress. Abstract: Polyphenol-rich functional foods have shown promise in ameliorating NAFLD but the relative effectiveness and mechanisms of different polyphenols are largely unknown. In a model of steatosis using HepG2 hepatocytes exposed to palmitic acid, we investigated the effect of selected polyphenols (resveratrol, quercetin, catechin, cyanidin, kuromanin) and berberine. Exposure to palmitic acid produced steatosis and intracellular ROS production, which were prevented by all of the polyphenols and berberine, at 10 µM. Palmitic acid produced a 245% increase in mRNA for inducible nitric oxide synthase ( iNOS ) that was almost completely prevented by all of the polyphenols (but not by berberine). Most of the polyphenols also partially inhibited palmitic acid-induced increases in markers of endoplasmic reticulum stress, and decreases in mitochondrial content and mitochondrial membrane potential. In conclusion, the polyphenols all similarly prevented steatosis, ROS generation and iNOS induction, and protected against ER stress and mitochondrial impairment.