• Izabelle Barcellos Santos, Graziele Freitas de Bem, Cordeiro Viviane Silva Cristino VSC Department of Pharmacology, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil., Cristiane Aguiar da Costa, de Carvalho Lenize Costa Reis Marins LCRM Department of Pharmacology, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil., Ana Paula Machado da Rocha, Gisele França da Costa, Dayane Teixeira Ognibene, Roberto Soares de Moura, and Angela Castro Resende.
• Department of Pharmacology, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
• Nutr Res. 2017 Jul 1; 43: 69-81.

AbstractNonalcoholic fatty liver disease is one of the most common complications of obesity. The Vitis vinifera L. grape skin extract (ACH09) is an important source of polyphenols, which are related to its antioxidant and antihyperglycemic activities. We hypothesized that ACH09 could also exert beneficial effects on metabolic disorders associated with obesity and evaluated ACH09's influence on high-fat (HF) diet-induced hepatic steatosis and insulin resistance in C57BL/6 mice. The animals were fed a standard diet (10% fat, control) or an HF diet (60% fat, HF) with or without ACH09 (200mg/[kg d]) for 12weeks. Our results showed that ACH09 reduced HF diet-induced body weight gain, prevented hepatic lipid accumulation and steatosis, and improved hyperglycemia and insulin resistance. The underlying mechanisms of these beneficial effects of ACH09 may involve the activation of hepatic insulin-signaling pathway because the expression of phosphorylated insulin receptor substrate-1, phosphatidylinositol 3-kinase, phosphorylated Akt serine/threonine kinase 1, and glucose transporter 2 was increased by ACH09 and correlated with improvement of hyperglycemia, hyperinsulinemia, and insulin resistance. ACH09 reduced the expression of the lipogenic factor sterol regulatory-element binding protein-1c in the liver and upregulated the lipolytic pathway (phosphorylated liver kinase B1/phosphorylated adenosine-monophosphate-activated protein kinase), which was associated with normal hepatic levels of triglyceride and cholesterol and prevention of steatosis. ACH09 prevented the hepatic oxidative damage in HF diet-fed mice probably by restoration of antioxidant activity. In conclusion, ACH09 protected mice from HF diet-induced obesity, insulin resistance, and hepatic steatosis. The regulation of hepatic insulin signaling pathway, lipogenesis, and oxidative stress may contribute to ACH09's protective effect.Copyright © 2017 Elsevier Inc. All rights reserved.

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