Obesity is typically linked to oxidative stress and inflammation, which lead to vascular damage and initiate the progression of atherosclerosis. The aim of this study was to determine the anti-atherosclerotic effect of orlistat on obesity-induced vascular oxidative stress in obese male rats. Twenty-four male Sprague–Dawley rats were categorized into two groups: normal (Normal group, n = 6) and high-fat diet (HFD group, n = 12). After six weeks, obese rats in the HFD group were administered either with distilled water (OB group) or orlistat 10 mg/kg/day (OB/OR group) for another six weeks. The OB group had a significant increase in lipid profiles (total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL)) and decrease in high-density lipoprotein (HDL) level compared to the Normal group. The aortic antioxidants enzymes activities (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and catalase (CAT)) as well as total glutathione (GSH) and total antioxidant capacity (TAC) of the OB group were significantly decreased compared to the Normal group. Furthermore, pro-inflammatory atherosclerotic markers (tumour necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1)) expressions were increased significantly, and anti-inflammatory marker (interleukin-10 (IL-10)) was decreased significantly in the OB group compared to the Normal group. Treatment with orlistat significantly improved lipid profile, increased antioxidant enzymes and expression of anti-inflammatory markers, and decreased the expression of the pro-inflammatory marker compared to the OB group. These findings may suggest the therapeutic effect of orlistat in attenuating the progression of the atherosclerotic stage in obesity.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid closely linked with many metabolic disorders, oxidative stress and inflammation. We aimed to evaluate the hepatoprotective effect of bee bread on oxidative stress and inflammatory parameters in MAFLD rats. Twenty-eight male Sprague-Dawley rats were assigned into four groups (n = 7/group): normal control (NC), high-fat diet (HFD), bee bread (HFD + Bb, HFD + 0.5 g/kg/day bee bread) and orlistat (HFD + Or, HFD + 10 mg/kg/day orlistat) groups. After 12 weeks, the HFD group demonstrated significantly higher body weight gain, serum levels of lipids (TG, TC, LDL), liver enzymes (AST, ALT, ALP) and adiponectin, liver lipids (TG, TC) and insulin resistance (HOMA-IR). Furthermore, the HFD group showed significantly decreased antioxidant enzyme activities (GPx, GST, GR, SOD, CAT) and GSH level, and increased liver oxidative stress (TBARS, NO), translocation of Nrf2 to the nucleus, Keap1 expression and inflammation (TNF-α, NF-κβ, MCP-1) together with histopathological alterations (steatosis, hepatocyte hypertrophy, inflammatory cell infiltration, collagen deposition), which indicated the presence of non-alcoholic steatohepatitis (NASH) and fibrosis. Bee bread significantly attenuated all these changes exerted by HFD feeding. In conclusion, our results suggest that bee bread might have antioxidant, anti-inflammatory, anti-steatotic and anti-fibrotic effects that are beneficial in protecting liver progression towards NASH and fibrosis.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an excessive buildup of liver lipids closely associated with various kinds of undesirable metabolic effects and oxidative stress. We aimed to investigate the protective and therapeutic effects of orlistat on metabolic syndrome and oxidative stress parameters in high-fat diet (HFD) induced-MAFLD rats. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6/group), i.e., Normal control (N), HFD, HFD + orlistat (HFD + O) (10 mg/kg/day administered concomitantly for 12 weeks as a protective model), and obese+orlistat (OB + O) (10 mg/kg/day administered 6 weeks after induction of obesity as a therapeutic model) groups. After 12 weeks, the HFD group had significantly increased Lee obesity index, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride, low-density lipoprotein levels, liver total cholesterol and triglyceride levels, insulin resistance and non-alcoholic steatohepatitis (NASH) together with decreased serum high-density lipoprotein level. Additionally, the HFD group also showed increased Nrf2 translocation to the nucleus with high Keap1 expression and increased liver oxidative stress parameters. Orlistat significantly improved all these alterations in HFD rats. We demonstrated that orlistat might have protective and therapeutic effects against HFD-induced MAFLD rats by its activation on Nrf2 signaling pathway, which subsequently improved metabolic syndrome and oxidative stress parameters.