Consumption of Quercetin and Quercetin-Containing Apple and Cherry Extracts Affects Blood Glucose Concentration, Hepatic Metabolism, and Gene Expression Patterns in Obese C57BL/6J High Fat-Fed Mice

Abstract

Background: Intake of polyphenols and polyphenol-rich fruit extracts has been shown to reduce markers of inflammation, diabetes, and hepatic complications that result from the consumption of a high-fat (HF) diet.

Objective: The objective of this study was to determine whether mice fed polyphenol-rich apple peel extract (AE), cherry extract (CE), and quercetin, a phytochemical abundant in fruits including apples and cherries, would modulate the harmful effects of adiposity on blood glucose regulation, endocrine concentrations, and hepatic metabolism in HF-fed C57BL/6J male mice.

Methods: Groups of 8-wk-old mice (n = 8 each) were fed 5 diets for 10 wk, including low-fat (LF; 10% of total energy) and HF (60% of total energy) control diets and 3 HF diets containing polyphenol-rich AE, CE, and quercetin (0.2% wt:wt). Also, an in vitro study used HepG2 cells exposed to quercetin (0-100 μmol/L) to determine whether intracellular lipid accumulation could be modulated by this phytochemical.

Results: Mice fed the HF control diet consumed 36% more energy, gained 14 g more body weight, and had ∼50% elevated blood glucose concentrations (all P < 0.05) than did LF-fed mice. Mice fed HF diets containing AE, CE, or quercetin became as obese as HF-fed mice, but had significantly lower blood glucose concentrations after food deprivation (-36%, -22%, -22%, respectively; P < 0.05). Concentrations of serum C-reactive protein were reduced 29% in quercetin-fed mice compared with HF-fed controls (P < 0.05). A qualitative evaluation of liver tissue sections suggested that fruit phytochemicals may reduce hepatic lipid accumulation. A quantitative analysis of lipid accumulation in HepG2 cells demonstrated a dose-dependent decrease in lipid content in cells treated with 0-100 μmol quercetin/L (P < 0.05).

Conclusions: In mice, consumption of AE, CE, or quercetin appears to modulate some of the harmful effects associated with the consumption of an obesogenic HF diet. Furthermore, in a cell culture model, quercetin was shown to reduce intracellular lipid accumulation in a dose-dependent fashion.

Keywords: C57BL/6J mice; PPAR-α; apples; cherries; high-fat diet; phytochemicals; polyphenols; quercetin.

FIGURE 1

Final body weight (A) and weekly energy intake (B) of male C57BL/6J mice fed an LF diet or HF diet alone or an HF diet containing apple peel extract, cherry extract, or quercetin for 10 wk. Energy intake was measured as a total for each group over the course of the study. Values are means ± SEMs, n = 8. Means without a common letter differ, P < 0.05. HF, high-fat; HF+AE, HF plus 0.2% apple peel extract; HF+CE, HF plus 0.2% cherry extract; HF+QUE, HF plus 0.2% quercetin; LF, low-fat.

FIGURE 2

Glucose concentration (A) and glucose tolerance (B) after food deprivation of male C57BL/6J mice fed an LF diet or HF diet alone or an HF diet containing apple peel extract, cherry extract, or quercetin for 6 wk. Mice were food-deprived 6 h before baseline blood glucose measurement. Values are means ± SEMs, n = 8. Means without a common letter differ, P < 0.05. *Tended to differ from HF when only HF-fed groups were compared, 0.05 < P < 0.01. HF, high-fat; HF+AE, HF plus 0.2% apple peel extract; HF+CE, HF plus 0.2% cherry extract; HF+QUE, HF plus 0.2% quercetin; LF, low-fat.

FIGURE 3

Cpt1a (A), Acox1 (B), and Scd1 (C) mRNA levels in male C57BL/6J mice fed an LF diet or HF diet alone or an HF diet containing apple peel extract, cherry extract, or quercetin for 10 wk. Values are normalized to Rpl30 gene expression and are expressed as a fold difference compared with the HF control diet. Values are means ± SEMs, n = 4–8. Means without a common letter differ, P < 0.05. Acox1, acyl-CoA oxidase 1; Cpt1a, Carnitine palmitoyltransferase 1α HF, high-fat; HF+AE, HF plus 0.2% apple peel extract; HF+CE, HF plus 0.2% cherry extract; HF+QUE, HF plus 0.2% quercetin; Rpl30, ribosomal protein L30; Scd1, stearoyl-CoA desaturase 1.

FIGURE 4

Liver histology stained with trichrome from male C57BL/6J mice fed an LF diet or HF diet alone or an HF diet containing apple peel extract, cherry extract, or quercetin for 10 wk. White globules within cells identify lipid accumulation. Scale: 0.5 inch = 50 μm. HF, high-fat; HF+AE, HF plus 0.2% apple peel extract; HF+CE, HF plus 0.2% cherry extract; HF+QUE, HF plus 0.2% quercetin; LF, low-fat.

FIGURE 5

Oil Red O staining of HepG2 cells exposed to oleic acid and various concentrations (0–100 μmol/L) of quercetin for 24 h. Intracellular lipid accumulation was measured. Values are means ± SEMs, n = 8. Means without a common letter differ, P < 0.05. QUE, quercetin.