(m-CF₃-PhSe)₂ counteracts metabolic disturbances and hypothalamic inflammation in a lifestyle rodent model

An unhealthy lifestyle is associated with metabolic disorders and neuroinflammation. In this study, the efficacy of m-trifluoromethyl-diphenyl diselenide [(m-CF₃-PhSe)₂] against lifestyle model-related metabolic disturbances and hypothalamic inflammation in young mice was investigated. From postnatal day 25 (PND25) to 66, male Swiss mice were subjected to a lifestyle model, an energy-dense diet (20:20% lard: corn syrup) and sporadic ethanol (3x/week). Ethanol was administrated intragastrically (i.g., 2 g/kg) to mice from PND45 to 60. From PND60 to 66, mice received (m-CF₃-PhSe)₂ (5 mg/kg/day; i. g). (m-CF₃-PhSe)₂ reduced relative abdominal adipose tissue weight, hyperglycemia, and dyslipidemia in mice exposed to the lifestyle-induced model. (m-CF₃-PhSe)₂ normalized hepatic cholesterol and triglyceride levels, and the activity of G-6-Pase increased in lifestyle-exposed mice. (m-CF₃-PhSe)₂ was effective in modulating hepatic glycogen levels, citrate synthase and hexokinase activities, protein levels of GLUT-2, p-IRS/IRS, p-AKT/AKT, redox homeostasis, and inflammatory profile of mice exposed to a lifestyle model. (m-CF₃-PhSe)₂ counteracted hypothalamic inflammation and the ghrelin receptor levels in mice exposed to the lifestyle model. (m-CF₃-PhSe)₂ reversed the decreased levels of GLUT-3, p-IRS/IRS, and the leptin receptor in the hypothalamus of lifestyle-exposed mice. In conclusion, (m-CF₃-PhSe)₂ counteracted metabolic disturbances and hypothalamic inflammation in young mice exposed to a lifestyle model.