Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia

The aim of this study was to assess the effect of the micronutrient selenium, as inorganic selenite, on adipocytes differentiation, and to identify underlying molecular mechanisms to advance the understanding of basic cellular mechanisms associated with adipogenesis. The effect of sodium selenite (Na₂SeO₃) on cell viability (bromide 3-[4,5-dimethylthiazol-2-yl]-2,5-difeniltetrazol [MTT] assay) in preadipocytes, lipid accumulation (oil red O [ORO] assay) and intracellular reactive oxygen species (ROS, [NBT assay]) in mature adipocytes, as well as explore molecular mechanisms via gene expression analyses (real-time quantitative polymerase chain reaction), before and after differentiation, was investigated using 3T3-L1 murine preadipocytes. Selenite (100, 200, and 400 nM) significantly decreased lipid accumulation during differentiation compared with untreated adipocytes (P < 0.05, 0.001, and 0.01, respectively). Preadipocytes exposure (48 h) to selenite caused an increase in glutathione peroxidase 1 (Gpx1) gene expression in a dose-dependent manner. Adipogenesis significantly increased intracellular reactive oxygen species levels (P < 0.05) while decreasing gene expression of antioxidant enzymes (Gpx1: P < 0.05) and significantly increasing gene expression of regulators of lipid catabolism (type II iodothyronine deiodinase [Dio2], P < 0.01) and markers of differentiation (eg, selenium-binding protein 1 [Selenbp1], peroxisome proliferator activated receptor gamma [Pparg], CCAAT/enhancer binding protein alpha [Cebpa], and fatty acid binding protein 4 [Fab4]) compared with preadipocytes (P < 0.01, 0.01, 0.01, and 0.001, respectively). Selenite exposure (200 nM) caused a significant increase in Gpx1, selenoprotein W (Selenow) and selenoprotein P (Selenop) gene expression, in adipocytes compared with untreated ones (P < 0.01, 0.001, and 0.05, respectively) with a significant decrease in heme oxygenase 1 (Ho-1), cyclooxygenase 2 (Cox2), Dio2, and Fabp4 gene expression (P < 0.001, 0.05, 0.05, and 0.01, respectively). Selenium, as selenite, prevented adipogenesis through increasing antioxidant selenoprotein expression, leading to decreased inflammatory markers and, subsequently, to a decrease in differentiation and lipid deposition. These findings, if demonstrated in vivo, could provide valuable data for novel dietary approaches to prevent obesity.

Nuclear Factor kappa B (NF-κB) is a key transcriptional regulator that plays important roles in the pathogenesis of hepatic inflammation and fibrosis in chronic liver diseases. NF-κB activation leads to production of pro-inflammatory and fibrogenic cytokines. Glycyrrhizin (GL) is reported to suppress liver fibrosis and cirrhosis. Omega-3 fatty acids (ω-3) play an anti-inflammatory role and they are reported to decrease hepatic injury in Thioacetamide (TAA) fibrotic model. We investigated the effects of GL and ω-3 on liver inflammation and fibrosis in rats and clarified the effects of these natural compounds on NF-κB level. 50 male Wistar rats randomized to 5 groups: Control group and 4 groups received TAA 200 mg/kg i.p. twice weekly for 8 weeks: TAA group, GL group (received GL 25 mg/kg daily by oral tube), ω-3 group (received ω-3150 mg/kg daily by oral tube), (GL+ω-3) group (received similar combined doses of both natural compounds). GL and ω-3 alone or in combination protected the liver from TAA hepatotoxic effects as they significantly decreased serum AST activity and serum total bilirubin level, they also significantly increased serum albumin and total protein levels. The hepatoprotective effects of GL and ω-3 were confirmed by the histopathological analysis as they significantly reduced the necroinflammatory scores and the extent of fibrosis. GL and ω-3 significantly decreased liver malondialdehyde level (P < 0.005), liver NF-ƙB level (P < 0.005) and its tissue expression as detected by immunohistochemistry. In conclusion, glycyrrhizin and omega-3 fatty acids alone or in combination have potent anti-inflammatory, anti-oxidant and anti-fibrotic effects