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Fanconi Anemia (FA) is a rare genetic disorder associated with a bone-marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents. Majority of the 15 FA genes and encoded proteins characterized so far are integrated into DNA repair pathways, however, other important functions cannot be excluded. FA cells are sensitive to oxidants, and accumulation of oxidized proteins has been characterized for several FA subgroups. Clinical phenotypes of both FA and other closely related diseases suggest altered functions of mitochondria, organelles responsible for cellular energetic metabolism, and also serving as an important producer and the most susceptible target from reactive oxidative species (ROS). In this study, we have shown that elevated level of mitochondrial ROS in FA cells is in parallel with the decrease of mitochondrial membrane potential, the decrease of ATP production, impaired oxygen uptake and pathological changes in the morphology of mitochondria. This is accompanied by inactivation of enzymes that are essential for the energy production (F1F0ATPase and cytochrome C oxidase) and detoxification of ROS (superoxide dismutase, SOD1). In turn, overexpression of SOD1 could rescue oxygen consumption rate in FA-deficient cells. Importantly, the depletion of mitochondria improved survival rate of mitomycin C treated FA cells suggesting that hypersensitivity of FA cells to chemotherapeutic drugs could be in part due to the mitochondria-mediated oxidative stress. On the basis of our results, we propose that deficiency in FA genes lead to disabling mitochondrial ROS-scavenging machinery further affecting mitochondrial functions and suppressing cell respiration.

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Background: Obesity is a major risk factor in the development of hepatic insulin resistance, which is characterized by an impairment of insulin ability to inhibit glucose output. Although the underlying mechanism for the link between obesity and insulin resistance in the liver is unclear, it has been widely reported and suggested that hepatic endoplasmic reticulum (ER) stress and inflammation induced by obesity lead to the development of hepatic insulin resistance and gluconeogenesis. Summary: This review addresses the aspects of ER stress and inflammation currently understood to be involved in metabolic disease, including their role in obesity, hepatic insulin resistance, and hyperglycemia.

BackgroundEven though Curcuma longa L. possesses various biological activities, it has strong flavor and taste, which decrease consumer palatability and limit industrial applications in food.ObjectiveThe present study investigates the effects of C. longa L. fermented with Aspergillus oryzae supplementation in 60% high-fat diet-induced obese rats measured by the activation of adipogenesis and lipolysis.DesignRats were divided into four groups (n=6 per group) after 1 week of acclimatization: a normal diet group comprised rats fed the AIN76A rodent diet; a high-fat diet-induced obese group with rats fed a 60% high-fat diet; a Garcinia cambogia treated group (positive control) with rats fed a 60% high-fat diet with G. cambogia 500 g/kg body weight (b.w.)/day; and an fermented C. longa L. 50% ethanolic extract treated group (FCE50) with rats fed a 60% high-fat diet with FCE50 500 g/kg b.w./day. Each group received the appropriate vehicle or sample daily by gastric intubation for 12 weeks.ResultsWe found that FCE50 administration suppressed b.w. gain and reduced white adipose tissue weight, serum triglyceride (TG), and cholesterol in high-fat diet-induced obese rats. These results can be associated with the suppression of adipocyte differentiation and lipogenesis with a decrease in the mRNA expressions of fatty acid synthase, acetyl-CoA carboxylase, adipocyte protein 2, and lipoprotein lipase induced by FCE50 administration. In addition, FCE50 increased lipolysis and β-oxidation by up-regulating the expression of lipases such as adipose triglyceride lipase, hormone-sensitive lipase, adiponectin, and AMP-activated protein kinase.ConclusionsThese results suggest that FCE50 can be a candidate for the prevention of obesity via suppressing adipogenesis and promoting lipolysis.

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