title: 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.
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.
authors.affiliation: Nutrition Research Center, Department of Community Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Nameni
authors.affiliation: Student Research Committee, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Hajiluian
authors.affiliation: Department of Physiology, School of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Parviz
authors.initials: P
authors.lastname: Shahabi
authors.affiliation: Nutrition Research Center, Department of Community Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran. abbasalizad_m@yahoo.com.
authors.forename: Mahdieh Abbasalizad
authors.initials: MA
authors.lastname: Farhangi
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mehran
authors.initials: M
authors.lastname: Mesgari-Abbasi
authors.affiliation: Pathology Section Social Security of East Azarbaijan, Alinasab Hospital, Tabriz, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Hemmati
authors.affiliation: Neurosciences Research Center, Tabriz University of Medical Science, Tabriz, Iran.
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Vatandoust
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D004435:Eating / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000097:blood* / Q000134:cerebrospinal fluid; D008297:Male; D009765:Obesity / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014807:Vitamin D / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D014807:Vitamin D
keywords: Insulin; Neurodegeneration; Obesity; TNF-α; Vitamin D