Obesity is a public health problem characterized by increased accumulation of fat into adipose tissues leading to oxidative stress, dyslipidemia, and chronic inflammatory status. We used an experimental model of high-fat diet-induced obesity to analyze the link between dyslipidemia, oxidative stress, and fat accumulation into adipose tissue of rats, as well as the involvement of intracellular mediators such as transition metals on signal transduction. We also looked at the ability of a grape seed and skin extract (GSSE) from a Tunisian cultivar to prevent fat-induced disturbances. Data showed that a high-fat diet (HFD) provoked dyslipidemia into plasma which is linked to an oxidative stress, an accumulation of transition metals such as manganese, copper, and zinc and a depletion of iron. GSSE prevented dyslipidemia by modulating lipase activity, together with increased antioxidant capacity and depletion of transition metals as well as of free radicals such as O2 (-) and OH. These data indicated that GSSE has important preventive effects on HFD-induced obesity and oxidative stress whose transduction seems to involve transition metals. GSSE should be used as a safe anti-obesity agent that could find potential applications in metabolic disorders involving transition metals dyshomeostasis.

Obesity is a tremendous public health problem, characterized by ectopic accumulation of fat into non-adipose tissues, leading to oxidative stress and chronic inflammation, in which the heart is the most severely affected organ. We used an experimental model of high-fat-diet (HFD)-induced obesity to analyze the link between oxidative stress and heart dysfunction. We also studied the cardioprotective effect of a grape seed and skin extract (GSE). Exposure of rats to HFD during 45 days induced heart hypertrophy, inflammation as assessed by plasma CRP elevation and contractile dysfunction as revealed after ischemia/reperfusion of Langendorff-perfused hearts. HFD also induced cardiac steatosis and lipotoxicity, which are linked to an oxidative stress status, worsened by increased siderosis and resulting in Ca(2+) overload. Importantly, GSE alleviated all the deleterious effects of HFD treatment. These studies suggest that GSE is a safe anti-obesity and cardioprotective agent that should also find potential applications in other inflammatory damaging conditions as stroke.

Obesity is related to an elevated risk of dementia and the physiologic mechanisms whereby fat adversely affects the brain are poorly understood. The present investigation analyzed the effect of a high fat diet (HFD) on brain steatosis and oxidative stress and the intracellular mediators involved in signal transduction, as well as the protection offered by grape seed and skin extract (GSSE). HFD induced ectopic deposition of cholesterol and phospholipid but not triglyceride. Moreover brain lipotoxicity is linked to an oxidative stress characterized by increased lipoperoxidation and carbonylation, inhibition of glutathione peroxidase and superoxide dismutase activities, depletion of manganese and a concomitant increase in ionizable calcium and acetylcholinesterase activity. Importantly GSSE alleviated all the deleterious effects of HFD treatment. Altogether our data indicated that HFD could find some potential application in the treatment of manganism and that GSSE should be used as a safe anti-lipotoxic agent in the prevention and treatment of fat-induced brain injury.