miR‐96 and autophagy are involved in the beneficial effect of grape seed proanthocyanidins against high‐fat‐diet‐induced dyslipidemia in mice

Abstract

We aimed to investigate the possible signaling pathways underlying the regulation of grape seed proanthocyanidins extracts (GSPE) on lipid metabolism. One hundred male C57BL/6 mice were divided into four groups: control group (normal diet), GSPE group (normal diet + GSPE), high-fat diet group (HFD), and high-fat diet plus GSPE (200 mg/ kg/day) group (HFD + GSPE). Mice received the diets for 180 days. Body weight and serum lipid levels were measured. Autophagic flux characteristics, such as accumulation of lipids, mitochondria, and autophagosomes in the liver, were detected using transmission electron microscopy. Expression profile of microRNAs (miRNAs) in the liver was determined using RNA microarray and quantitative real time polymerase chain reaction (qRt-PCR). GSPE significantly decreased the weight gain, serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol but increased high-density lipoprotein cholesterol in the HFD mice. Autophagic flux was significantly increased by HFD but decreased by GSPE treatment. GSPE significantly attenuated HFD-induced miR-96 upregulation, which in turn reduced the expressions of miR-96 downstream molecules, FOXO1, mTOR, p-mTOR, and LC3A/B. These results suggested that the miR-96 is involved in the protective effect of GSPE against HFD-induced dyslipidemia. Possible mechanisms might be through mTOR and FOXO1, which facilitate autophagic flux for clearance of lipid accumulation. KEYWORDS autophagic flux, dyslipidemia, grape seed proanthocyanidins extracts (GSPE), high-fat diet (HFD), miR-96, mTOR

Grape-Seed Proanthocyanidin Extract Reverts Obesity-Related Metabolic Derangements in Aged Female Rats

“…In previous studies of young, female rats [ 37 , 43 ], all GSPE treatments ameliorated dyslipidaemia and the insulin-resistant state of obese rats. Other studies have also shown that GSPE protects against disorders in mice induced by a high-fat diet [ 44 ]. Contrary to our results, a dietary dose of GSPE (25 mg/kg BW) managed to reduce the plasma levels of triglycerides, glucose, and insulin in cafeteria-diet-fed male rats [ 45 ], while puerarin [ 46 ], resveratrol [ 47 ], and procyanidin B2 [ 17 ] ameliorated hyperglycaemia and hyperinsulinemia caused by an obesogenic diet.…”

Grape Seed Procyanidin B2 Protects Porcine Ovarian Granulosa Cells against Oxidative Stress-Induced Apoptosis by Upregulating let-7a Expression

“…Recent studies have shown that grape seed proanthocyanidin extract (GSPE) alleviates oxidative damage in mouse testis and liver by activating Nrf2 signaling [46, 47]. Another study demonstrated that GSPE can reduce high-fat-diet- (HFD-) induced dyslipidemia in mice by attenuating the HFD-induced upregulation of miR-96 expression [48]. We previously found that GSPB2 alleviates oxidative stress-induced GC apoptosis by evoking an autophagic response [26].…”

MicroRNAs: The Link between the Metabolic Syndrome and Oncogenesis

“…Induction of miR-96 by dietary saturated fatty acids impairs insulin signaling and exacerbates hepatic insulin resistance through the suppression of INSR and IRS-1 [276]. Grape seed proanthocyanidins extracts significantly decreases HFDinduced miR-96 upregulation in mice, and reduces the expressions of miR-96 downstream molecules, FOXO1, p-mTOR, mTOR, and LC3A/B [277].…”