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The Impact of Vitamin D Supplementation on Neurodegeneration, TNF-α Concentration in Hypothalamus, and CSF-to-Plasma Ratio of Insulin in High-Fat-Diet-Induced Obese Rats

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Abstract

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 obesity-promoting 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, vitamin D 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-diet-induced obese rats. Further studies are needed to better clarify the underlying mechanisms.

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Authors and Affiliations

  1. Nutrition Research Center, Department of Community Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran

    Ghazaleh Nameni & Mahdieh Abbasalizad Farhangi

  2. Student Research Committee, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran

    Ghazaleh Hajiluian

  3. Department of Physiology, School of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Parviz Shahabi

  4. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mehran Mesgari-Abbasi

  5. Pathology Section Social Security of East Azarbaijan, Alinasab Hospital, Tabriz, Iran

    Mohammad-Reza Hemmati

  6. Neurosciences Research Center, Tabriz University of Medical Science, Tabriz, Iran

    Seyed Mahdi Vatandoust

Authors
  1. Ghazaleh Nameni
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  2. Ghazaleh Hajiluian
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  3. Parviz Shahabi
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  4. Mahdieh Abbasalizad Farhangi
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  5. Mehran Mesgari-Abbasi
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  6. Mohammad-Reza Hemmati
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  7. Seyed Mahdi Vatandoust
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Correspondence to Mahdieh Abbasalizad Farhangi.

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The study protocol was approved by the Ethics Committee of Tabriz University Medical Sciences (TBZMED.REC.1394.747).

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The authors declare that they have no conflicts of interest.

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Nameni, G., Hajiluian, G., Shahabi, P. et al. The Impact of Vitamin D Supplementation on Neurodegeneration, TNF-α Concentration in Hypothalamus, and CSF-to-Plasma Ratio of Insulin in High-Fat-Diet-Induced Obese Rats. J Mol Neurosci 61, 247–255 (2017). https://doi.org/10.1007/s12031-016-0864-y

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