Full transcriptome analysis of gene expression in liver of mice in a comparative study of quercetin efficiency on two obesity models

Abstract

BACKGROUND: Quercetin (Q; 3,3',4',5,7 - pentahydroxyflavone) can help alleviate the pathological effects of nutritional obesity and metabolic syndrome when taken as part of products for special dietary needs and food supplements. The mechanisms of action of Q at the genetic level are not well understood.AIMS: To study gene expression in liver tissue of mice with alimentary and genetically determined obesity upon intake of Q with diet.MATERIALS AND METHODS: During 46 days of the experiment on 32 male C57Bl/6J mice fed a diet with an excess of fat and fructose and 24 male genetically obese db/db mice the effect of Q in dose of 25 or 100 mg/kg of body weight was studied on differential expression of 39430 genes in mice livers by full transcriptome profiling on microchip according to the Agilent One-Color Microarray-Based Gene Expression Analysis Low Input Quick Amp Labeling protocol (version 6.8). To identify metabolic pathways (KEGGs) that were targets of Q exposure, transcriptomic data were analyzed using bioinformatics methods in an “R” environment.RESULTS: Differences were revealed in the nature of Q supplementation action in animals with dietary induced and genetically determined obesity on a number of key metabolic pathways, including the metabolism of lipids and steroids (Saa3, Cidec, Scd1, Apoa4, Acss2, Fabp5, Car3, Acacb, Insig2 genes), amino acids and nitrogen bases (Ngef, Gls2), carbohydrates (G6pdx, Pdk4), regulation of cell growth, apoptosis and proliferation (Btg3, Cgref1, Fst, Nrep Tuba8), neurotransmission (Grin2d, Camk2b), immune system reactions (CD14i, Jchain, Ifi27l2b).CONCLUSIONS: The data obtained help to explain the ambiguous effectiveness of Q, like other polyphenols, in the dietary treatment of various forms of obesity in humans, as well as to form a set of sensitive biomarkers that allow us to elucidate the effectiveness of minor biologically active food substances in preclinical trials of new means of metabolic correction of obesity and metabolic syndrome.