Abstract
Objectives:
The purpose of this research was to investigate the effects of vitamin D administration on cognitive function, nuclear factor-κB (NF-κB), brain-derived neurotrophic factor (BDNF) concentration in the hippocampus and blood–brain barrier (BBB) permeability in high-fat diet (HFD)-induced obese rats.
Methods:
Male Wistar rats were fed either a control diet or HFD for 16 weeks (n=20); then, each group was randomized into two subgroups supplemented orally with 500 IU kg−1 vitamin D for 5 weeks. A Morris water maze (MWM) test was performed at the 21st week to examine cognitive function. BBB permeability was characterized by Evans blue dye in the hippocampus. BDNF and NF-κB concentrations in the hippocampus and serum vitamin D concentrations were also measured.
Results:
HFD led to a significant delay in escape latency time and reduced time of MWM probe test because of increased NF-κB and decreased BDNF concentrations in the hippocampus. Vitamin D supplementation in the HFD group significantly reduced body weight, NF-κB concentrations, BBB permeability and increased BDNF concentrations in the hippocampus.
Conclusions:
Vitamin D reversed HFD-induced cognitive impairments by reduction of the NF-κB and elevation of BDNF concentrations and modulation of the BBB permeability in rats’ hippocampus.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Jafari-Adli S, Jouyandeh Z, Qorbani M, Soroush A, Larijani B, Hasani-Ranjbar S . Prevalence of obesity and overweight in adults and children in Iran; a systematic review. J Diabetes Metab Disord 2014; 13: 121.
WHOObesity and Overweight. WHO: Geneva, Switzerland, Updated June 2016. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/.
Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384: 766–781.
Bray GA, Paeratakul S, Popkin BM . Dietary fat and obesity: a review of animal, clinical and epidemiological studies. Physiol Behav 2004; 83: 549–555.
Hariri N, Thibault L . High-fat diet-induced obesity in animal models. Nutr Res Rev 2010; 23: 270–299.
Aballay LR, Eynard AR, del Pilar Díaz M, Navarro A, Muñoz SE . Overweight andobesity: a review of their relationship to metabolic syndrome, cardiovascular disease, and cancer in South America. Nutr Rev 2013; 71: 168–179.
Anstey K, Cherbuin N, Budge M, Young J . Body mass index in midlife and late‐life as a risk factor for dementia: a meta‐analysis of prospective studies. Obes Rev 2011; 12: e426–e437.
Miller AA, Spencer SJ . Obesity and neuroinflammation: a pathway to cognitive impairment. Brain Behav Immun 2014; 42: 10–21.
Liu Y, Fu X, Lan N, Li S, Zhang J, Wang S et al. Luteolin protects against high fat diet-induced cognitive deficits in obesity mice. Behav Brain Res 2014; 267: 178–188.
Li W, Prakash R, Chawla D, Du W, Didion SP, Filosa JA et al. Early effects of high-fat diet on neurovascular function and focal ischemic brain injury. Am J Physiol Regul Integr Comp Physiol 2013; 304: R1001–R1008.
Nerurkar PV, Johns LM, Buesa LM, Kipyakwai G, Volper E, Sato R et al. Momordica charantia (bitter melon) attenuates high-fat diet-associated oxidative stress and neuroinflammation. Neuroinflamm J 2011; 8: 2094–2098.
Greenwood CE, Winocur G . High-fat diets, insulin resistance and declining cognitive function. Neurobiol Aging 2005; 26: 42–45.
Krause DL, Müller N . Neuroinflammation, microglia and implications for anti-inflammatory treatment in Alzheimer's disease. Int J Alzheimers Dis 2010; 14: 732806–732815.
Mattson M, Meffert M . Roles for NF-κB in nerve cell survival, plasticity, and disease. Cell Death Differ 2006; 13: 852–860.
Zhang X, Dong F, Ren J, Driscoll MJ, Culver B . High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex. Exp Neurol 2005; 191: 318–325.
Park HR, Park M, Choi J, Park KY, Chung HY, Lee J . A high-fat diet impairs neurogenesis: involvement of lipid peroxidation and brain-derived neurotrophic factor. Neurosci lett 2010; 482: 235–239.
Bekinschtein P, Cammarota M, Izquierdo I, Medina JH . Reviews: BDNF and memory formation and storage. J Neurosci 2008; 14: 147–156.
Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D . New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 2002; 13: 100–105.
Przybelski RJ, Binkley NC . Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function. Arch Biochem Biophys 2007; 460: 202–205.
Lee DM, Tajar A, Ulubaev A, Pendleton N, O’Neill TW, O’Connor DB et al. Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men. J Neurol Neurosurg Psychiatry 2009; 80: 722–729.
Smolders J, Damoiseaux J, Menheere P, Hupperts R . Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol 2008; 194: 7–17.
Pogge E . Vitamin D and Alzheimer's disease: is there a link? Consultant Pharmacist 2010; 25: 440–450.
Emamat H, Noori M, Foroughi F, Rismanchi M, Eini–Zinab H, Hekmatdoost A . An accessible and pragmatic experimental model of nonalcoholic fatty liver disease. Middle East J Dig Dis 2016; 8: 109–115.
Alrefaie Z . Vitamin D 3 improves decline in cognitive function and cholinergic transmission in prefrontal cortex of streptozotocin-induced diabetic rats. Behav Brain Res 2015; 287: 156–162.
Esen F, Erdem T, Aktan D, Orhan M, Kaya M, Eraksoy H et al. Effect of magnesium sulfate administration on blood–brain barrier in a rat model of intraperitoneal sepsis: a randomized controlled experimental study. Crit Care 2004; 9: 1.
Terrando N, Eriksson LI, Kyu Ryu J, Yang T, Monaco C, Feldmann M et al. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol 2011; 70: 986–995.
Pi‐Sunyer FX . The obesity epidemic: pathophysiology and consequences of obesity. Obes Res 2002; 10 (Suppl. 12): 97S–104S.
Pistell PJ, Morrison CD, Gupta S, Knight AG, Keller JN, Ingram DK et al. Cognitive impairment following high fat diet consumption is associated with brain inflammation. J Neuroimmunol 2010; 219: 25–32.
Kanoski SE, Davidson TL . Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiol Behav 2011; 103: 59–68.
Smith E, Hay P, Campbell L, Trollor JN . A review of the association between obesity and cognitive function across the lifespan: implications for novel approaches to prevention and treatment. Obes Rev 2011; 12: 740–755.
Smolders J, Moen SM, Damoiseaux J, Huitinga I, Holmøy T . Vitamin D in the healthy and inflamed central nervous system: access and function. J Neurol Sci 2011; 311: 37–43.
Kalueff AV, Eremin KO, Tuohimaa P . Mechanisms of neuroprotective action of vitamin D3. Biochemistry (Moscow) 2004; 69: 738–741.
Sharma S, Fulton S . Diet-induced obesity promotes depressive-like behaviour that is associated with neural adaptations in brain reward circuitry. Int J Obes 2013; 37: 382–389.
Watson AEN, Bruggeman EC, Parent MB . Wearing memory thin: the effects of high fat diet on neuroinflammation and memory. Discovery 2013; 1: 39–52.
Yin Y, Yu Z, Xia M, Luo X, Lu X, Ling W . Vitamin D attenuates high fat diet-induced hepatic steatosis in rats by modulating lipid metabolism. Eur J Clin Invest 2012; 42: 1189–1196.
Marcotorchino J, Tourniaire F, Astier J, Karkeni E, Canault M, Amiot MJ et al. Vitamin D protects against diet-induced obesity by enhancing fatty acid oxidation. J Nutr Biochem 2014; 25: 1077–1083.
Moghadamnia AA, Hakiminia S, Baradaran M, Kazemi S, Ashraf-pour M . Vitamin D improves learning and memory impairment in streptozotocin-induced diabetic mice. Arch Iran Med 2015; 18: 362–366.
Kiasalari Z, Khalili M, Shafiee S, Roghani M . The effect of vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats. Indian J Pharmacol 2016; 48: 11–14.
Bonizzi G, Karin M . The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends Immunol 2004; 25: 280–288.
Sun J, Kong J, Duan Y, Szeto FL, Liao A, Madara JL et al. Increased NF-κB activity in fibroblasts lacking the vitamin D receptor. Am J Physiol Endocrinol Metab 2006; 291: E315–E322.
Vanoirbeek E, Krishnan A, Eelen G, Verlinden L, Bouillon R, Feldman D et al. The anti-cancer and anti-inflammatory actions of 1, 25 (OH) 2 D 3. Best Pract Res Clin Endocrinol Metab 2011; 25: 593–604.
Ticinesi A, Meschi T, Lauretani F, Felis G, Franchi F, Pedrolli C et al. Nutrition and inflammation in older individuals: focus on vitamin D, n-3 polyunsaturated fatty acids and whey proteins. J Nutr 2016; 8: 186.
Erbaş O, Solmaz V, Aksoy D, Yavaşoğlu A, Sağcan M, Taşkıran D . Cholecalciferol (vitamin D3) improves cognitive dysfunction and reduces inflammation in a rat fatty liver model of metabolic syndrome. Life sci 2014; 103: 68–72.
Cordner ZA, Tamashiro KL . Effects of high-fat diet exposure on learning & memory. Physiol Behav 2015; 152 (Part B): 363–371.
Mohamed AR, Soliman GY, Ismail CA, Mannaa HF . Neuroprotective role of vitamin D3 in colchicine-induced Alzheimer’s disease in rats. Alexandria J Med 2015; 51: 127–136.
Pirotta S, Kidgell D, Daly R . Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial. Osteoporosis Int J 2014; 26: 131–140.
Van der Schaft J, Koek H, Dijkstra E, Verhaar H, van der Schouw Y, Emmelot-Vonk M . The association between vitamin D and cognition: a systematic review. Ageing Res Rev 2013; 12: 1013–1023.
Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med 2010; 170: 1135–1141.
Acknowledgements
This work was supported by a grant from the Tabriz University of Medical Sciences (Grant Number: TBZMED.REC.1394.784).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Hajiluian, G., Nameni, G., Shahabi, P. et al. Vitamin D administration, cognitive function, BBB permeability and neuroinflammatory factors in high-fat diet-induced obese rats. Int J Obes 41, 639–644 (2017). https://doi.org/10.1038/ijo.2017.10
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2017.10
This article is cited by
-
RETRACTED ARTICLE: Vitamin D alleviates cognitive dysfunction and brain damage induced by copper sulfate intake in experimental rats: focus on its combination with donepezil
Naunyn-Schmiedeberg's Archives of Pharmacology (2023)
-
Cognition enhancing abilities of vitamin D, epalrestat and their combination in diabetic rats with and without scopolamine induced amnesia
Cognitive Neurodynamics (2022)
-
Co-treatment of vitamin D supplementation with enriched environment improves synaptic plasticity and spatial learning and memory in aged rats
Psychopharmacology (2021)
-
The potential therapeutic effects of the gut microbiome manipulation by synbiotic containing-Lactobacillus plantarum on neuropsychological performance of diabetic rats
Journal of Translational Medicine (2020)
-
Cardiac tissue oxidative stress and inflammation after vitamin D administrations in high fat- diet induced obese rats
BMC Cardiovascular Disorders (2017)