Chardonnay Grape Seed Flour Ameliorates Hepatic Steatosis and Insulin Resistance via Altered Hepatic Gene Expression for Oxidative Stress, Inflammation, and Lipid and Ceramide Synthesis in Diet-Induced Obese Mice

Figures

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  Fig 1. Effect of Chardonnay grape seed flour (ChrSd) on (A) liver weight, (B) total hepatic lipid content, (C) hepatic oil red O-stained area (%) and (D) H & E (a, b, c, & d) and oil red O (e & f) staining of liver tissues of male diet-induced obese mice (DIO) fed high-fat (HF) diets containing 5% microcrystalline cellulose (MCC, control) or 10% (w/w) ChrSd for 5 weeks. Data are expressed as mean ± SE; n = 8–10/group. *P < 0.05.

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  Fig 2. Effect of Chardonnay grape seed flour (ChrSd) on (A) plasma lipids and (B) leptin concentration. Male diet-induced obese mice (DIO) were fed high-fat (HF) diets containing 5% microcrystalline cellulose (MCC, control) or 10% (w/w) ChrSd for 5 weeks, and blood was collected in a food-deprived state. VLDL, very low-density lipoprotein; LDL, low-density lipoprotein; HDL, high-density lipoprotein. Data are expressed as mean ± SE; n = 8–10/group. *P < 0.05.

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  Fig 3. Insulin tolerance in obese mice fed a high-fat (HF) diet supplemented with either 5% microcrystalline cellulose (MCC, control) or 10% (w/w) Chardonnay grape seed flour (ChrSd) for 5 weeks. (A) Insulin tolerance tests (ITTs) were performed in the fasting state. (B) Area under the curve (AUC) values. Data are expressed as mean ± SE. n = 8–9/group. *P < 0.05.

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  Fig 4. Reductions in Chi3l1, Sptlc3, and Aldh1a1 protein in livers from mice fed Chardonnay grape seed flour. (A) Western blots of Chi3l1, Sptlc3, and Aldh1a1 in protein extracts from livers of male, diet-induced obese mice (DIO) fed high-fat (HF) diets containing 5% microcrystalline cellulose (MCC, control) or 10% (w/w) ChrSd for 5 weeks. (B) Quantification of protein expression in (A). (C) DCF fluorescence intensity in the liver of male DIO mice fed HF diets containing 5% MCC or 10% ChrSd for 5 weeks. Data are expressed as mean ± SE; n = 3/group. *P < 0.05.

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  Fig 5. Proposed mechanisms by which flavonoid-rich Chardonnay grape seed flour (ChrSd) ameliorates high-fat (HF) diet-induced insulin resistance, hepatic steatosis, and nonalcoholic fatty liver disease (NAFLD). Supplementation with ChrSd lowers HF-induced insulin resistance and hepatic steatosis and enhances leptin sensitivity, followed by lowered oxidative stress and inflammation via reduction of ROS and ceramide synthesis. The result is possible amelioration of HF-induced progression of NAFLD. ROS, reactive oxygen species.