| There is growing evidence that obesity can lead to
neurodegeneration induced by pro-inflammatory cytokines such
as tumor necrosis factor (TNF-α). Moreover, obesity is associated
with reduced transport of insulin through the blood-brain
barrier (BBB). Insulin deficiency in the brain especially in the
hypothalamus region has neurodegenerative and obesitypromoting
effects. Because of the anti-inflammatory and neuroprotective
effects of vitamin D, in the current experimental study,
we aimed to investigate the effects of vitamin D supplementation
on neurodegeneration, TNF-α concentration in the hypothalamus,
and cerebrospinal fluid (CSF) to serum ratio of insulin in
high-fat-diet-induced obese rats. At the first phase of the study,
the rats were divided into two groups: (1) normal diet (ND, 10%
fat) and (2) high-fat diet (HFD, 59% fat) and were fed for
16 weeks. In the second phase, each group was subdivided into
four groups including the following: ND, normal diet + vitamin
D, HFD, and HFD + vitamin D. Weight was measured and
recorded weekly. Vitamin D supplementation for 5 weeks at
500 IU/kg dosage was used. One week after vitamin D supplementation,
daily food intake was recorded. At week 22, blood
was collected to determine fasting serum glucose, vitamin D, and
insulin concentrations, and the homeostasis model assessment of
insulin resistance (HOMA-IR) was calculated. CSF samples
were also collected to measure insulin concentrations, and the
hypothalamus was dissected to determine TNF-α concentration.
HFD significantly increased TNF-α concentrations and
degenerated neurons in the hypothalamus (P = 0.02). We also
observed a significant reduction of CSF-to-serum ratio of insulin
in HFD group (P = 0.03). The HOMA-IR test indicated significant
increment of insulin resistance in HFD-fed rats (P = 0.006).
Vitamin D supplementation in HFD group significantly reduced
weight (P = 0.001) and food intake (P = 0.008) and increased
CSF-to-serum ratio of insulin (P = 0.01). Furthermore, vitaminD
decreased insulin resistance in the HFD group (P = 0.008).
Vitamin D had no significant effect on degenerated neurons
and TNF-α concentration in the hypothalamus. According to
our findings, vitamin D improved brain insulin homeostasis
and modulated food intake and body weight in high-fat-dietinduced
obese rats. Further studies are needed to better clarify
the underlying mechanisms. |