Quercetin and green tea extract supplementation downregulates genes related to tissue inflammatory responses to a 12-week high fat-diet in mice

Abstract

Quercetin (Q) and green tea extract (E) are reported to counter insulin resistance and inflammation and favorably alter fat metabolism. We investigated whether a mixture of E + Q (EQ) could synergistically influence metabolic and inflammation endpoints in a high-fat diet (HFD) fed to mice. Male C57BL/6 mice (n = 40) were put on HFD (fat = 60%kcal) for 12 weeks and randomly assigned to Q (25 mg/kg of body weight (BW)/day), E (3 mg of epigallocatechin gallate/kg BW/day), EQ, or control groups for four weeks. At 16 weeks, insulin sensitivity was measured via the glucose tolerance test (GTT), followed by area-under-the-curve (AUC) estimations. Plasma cytokines and quercetin were also measured, along with whole genome transcriptome analysis and real-time polymerase chain reaction (qPCR) on adipose, liver, and skeletal muscle tissues. Univariate analyses were conducted via analysis of variance (ANOVA), and whole-genome expression profiles were examined via gene set enrichment. At 16 weeks, plasma quercetin levels were higher in Q and EQ groups vs. the control and E groups (p < 0.05). Plasma cytokines were similar among groups (p > 0.05). AUC estimations for GTT was 14% lower for Q vs. E (p = 0.0311), but non-significant from control (p = 0.0809). Genes for cholesterol metabolism and immune and inflammatory response were downregulated in Q and EQ groups vs. control in adipose tissue and soleus muscle tissue. These data support an anti-inflammatory role for Q and EQ, a result best captured when measured with tissue gene downregulation in comparison to changes in plasma cytokine levels.