Investigation of brain-derived neurotrophic factor (BDNF) gene expression in hypothalamus of obese rats: Modulation by omega-3 fatty acids

Purpose: The aim of this study was investigating the effect of omega-3 fatty acids (-3 FAs) on brain-derived neurotrophic factor (BDNF) gene expression, using in vivo and in vitro models, to unravel the potential mechanisms of polyunsaturated fatty acids use in obesity. Materials and methods: Twenty-nine Sprague-Dawley rats were divided into three groups; lean controls fed normal chow diet for 14 weeks, obese controls fed 60% of their diet as saturated fats for 14 weeks, and -3 FAs-treated rats fed 60% saturated fat diet for 14 weeks with concomitant oral administration of 400mg/kg/day -3 FAs, mainly docosahexaenoic acid and EPA, from week 12 to week 14. For the in vitro experiment, hypothalamic cells from six obese rats were cultured in the presence of different concentrations of -3 FAs to determine its direct effect on BDNF expression. Results: In vivo results showed that obesity has negative effect on BDNF gene expression in rat hypothalamus that was reversed by administration of -3 FAs. Obese rats showed hypercholesterolemia, hypertriglyceridemia, normoinsulinemia, hyperglycemia and hyperleptinemia. Treatment with -3 FAs showed significant decrease in serum total cholesterol and TAG. Also serum glucose level and HOMA index were decreased significantly. In vitro results demonstrated the increase in BDNF expression by -3 FAs in a dose-dependent manner. Conclusions: Obesity causes down-regulation of BDNF gene expression that can be reversed by -3 FAs treatment, making them an interesting treatment approach for obesity and metabolic disease.