Effects of physical activity and melatonin on brain-derived neurotrophic factor and cytokine expression in the cerebellum of high-fat diet-fed rats

Aims: Obesity suppresses brain-derived neurotrophic factor (BDNF) expression and increases the expression of pro-inflammatory cytokines. Herein, we assessed whether exercise training (ET), melatonin administration (MT), or their combination can affect the expressions of BDNF and cytokines in the cerebellum of high-fat diet (HFD)-fed rats.

Methods: Wistar rats (4 weeks old) were divided into five groups: normal diet (ND)-fed control (ND-SED), HFD-fed control (HFD-SED), HFD-fed ET (HFD-ET), HFD-fed MT (HFD-MT), and HFD-fed MT plus ET (HFD-ETMT) group. The rats were fed ND or HFD for 17 weeks. Rats were subjected to ET (running on a treadmill) and/or MT (melatonin 5 mg/kg body weight, i.p.) for 9 weeks, 8 weeks after beginning the diet intervention. Changes in BDNF and cytokine expression levels were determined using immunoblotting and cytokine arrays, respectively, 36 hours following the last bout of ET.

Results: Neither HFD-ET nor HFD-MT rats exhibited enhanced BDNF expression in the cerebellum, but HFD-ETMT rats had higher level of BDNF expression compared with the others. The expression of TrkB, a BDNF receptor, was higher in HFD-ETMT rats than in HFD-ET and HFD-MT rats. HFD enhanced the expression of interleukin (IL)-1, IL-2, and interferon-γ but reduced the expression of IL-4, IL-6, and IL13. ET and ET plus MT counteracted these HFD-induced changes in cytokine expressions.

Conclusion: Exercise in combination with melatonin confers the potential benefits of increasing BDNF and improving HFD-induced dysregulations of cytokines in the cerebellum.