Relationship between the thrombospondin-1/Toll-like receptor 4 (TSP1/TLR4) pathway and vitamin D levels in obese and normal weight subjects with different metabolic phenotypes.

Thrombospondin-1 (TSP1) contributes to obesity-associated inflammation via activating Toll-like receptor 4 (TLR4). The regulatory role of vitamin D on this pathway has been suggested. This study aimed to investigate the relationship between TSP1/TLR4 pathway and vitamin D in obese and normal weight subjects with different metabolic phenotypes. Thirty obese and thirty normal weight men were selected. Anthropometric parameters and serum TSP1, TLR4, TNF-α, vitamin D, and metabolic profile were determined. Metabolic phenotypes of obese and normal weight subjects were determined. Findings revealed enhanced TSP1/TLR4/TNF-α levels and reduced 25(OH)D levels in obese compared to normal weight subjects and metabolically unhealthy compared to metabolically healthy subjects. TSP1 correlated positively with parameters of unhealthy metabolic profile. TSP1, TLR4 and TNF-α levels significantly negatively correlated with vitamin D levels. In conclusion, vitamin D might exert a regulatory role on TSP1/TLR4 pathway, providing a potential mechanism that links hypovitaminosis D with risk of metabolic dysfunction.

Effect of exercise on the hypothalamic-pituitary-gonadal axis in a rat model of Alzheimer's disease.

Hypothalamic-pituitary-gonadal (HPG) axis dysregulation was suggested to play a crucial role in Alzheimer's disease (AD). This study investigated the effects of exercise on HPG hormones in an AD rat model, as a possible mechanism underlying the favorable effect of exercise on AD. Forty male Wistar albino rats 2-3 months old were subdivided randomly into two groups (n = 20 each): AD group (injected intraperitoneally with aluminum chloride (70 mg/kg/day) for 6 weeks) and Control group. Each group was subdivided into exercised or non-exercised group (n = 10 each). Exercised groups were subjected to a swimming protocol (60 min/day, 5 days/week, 4 weeks). Serum HPG hormones, hippocampal ß-amyloid levels and Morris water-maze cognition were assessed. Results demonstrated higher levels of ß-amyloid, gonadotropin releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) together with lower testosterone levels and cognitive impairment in the AD rats compared to controls. Β-amyloid levels negatively correlated with testosterone levels and positively correlated with GnRH, LH and FSH among the AD rats. Higher testosterone and lower GnRH, LH, FSH and ß-amyloid levels, as well as cognitive improvement, were observed in the exercised compared to non-exercised AD rats, suggesting a modulatory role of exercise training on AD-associated HPG axis dysregulation.

Protective effects of vitamin D on neurophysiologic alterations in brain aging: role of brain-derived neurotrophic factor (BDNF).

Background/aim: Vitamin D has been hypothesized to be main regulator of the aging rate, alongside evidences support its role in neuroprotection. However, data about the protective role of vitamin D against neurophysiologic alterations associated with brain aging is limited. This study investigated the possible protective effects that vitamin D has on brain-derived neurotrophic factor (BDNF), cholinergic function, oxidative stress and apoptosis in aging rat brain.Methods: Male Wister albino rats aged 5 months (young), 12 months (middle aged) and 24 months (old) (n = 20 each) were used. Each age group subdivided to either vitamin D3 supplementation (500 IU/kg/day orally for 5 weeks) or no supplementation (control) group (n = 10 each). Serum 25-hydroxyvitamin D [25(OH)D], brain BDNF and malondialdehyde levels and activities of acetylcholinesterase (AChE), antioxidant enzymes (glutathione reductase, glutathione peroxidase and superoxide dismutase) and caspase-3 were quantified.Results: Vitamin D supplementation significantly mitigated the observed aging-related reduction in brain BDNF level and activities of AChE and antioxidant enzymes and elevation in malondialdehyde level and caspase-3 activity compared to control groups. Brain BDNF level correlated positively with serum 25(OH) D level and brain AChE activity and negatively with brain malondialdehyde level and caspase-3 activity in supplemented groups.Conclusion: Restoring vitamin D levels may, therefore, represent a useful strategy for healthy brain aging. Augmenting brain BDNF seems to be a key mechanism through which vitamin D counteracts age-related brain dysfunction.