Obesity-related Cognitive Impairment: The Role of Endothelial Dysfunction

Overview

Journal Neurobiol Dis

Specialty Neurology

Date 2019 Aug 28

PMID 31454547

Citations 44

Authors

Joy Jones Buie

Luke S Watson

Crystal J Smith

Catrina Sims-Robinson

Affiliations

Soon will be listed here.

Abstract

Obesity is a global pandemic associated with macro- and microvascular endothelial dysfunction. Microvascular endothelial dysfunction has recently emerged as a significant risk factor for the development of cognitive impairment. In this review, we present evidence from clinical and preclinical studies supporting a role for obesity in cognitive impairment. Next, we discuss how obesity-related hyperinsulinemia/insulin resistance, systemic inflammation, and gut dysbiosis lead to cognitive impairment through induction of endothelial dysfunction and disruption of the blood brain barrier. Finally, we outline the potential clinical utility of dietary interventions, exercise, and bariatric surgery in circumventing the impacts of obesity on cognitive function.

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References

Zhang P, Yu Y, Qin Y, Zhou Y, Tang R, Wang Q . Alterations to the microbiota-colon-brain axis in high-fat-diet-induced obese mice compared to diet-resistant mice. J Nutr Biochem. 2019; 65:54-65. DOI: 10.1016/j.jnutbio.2018.08.016. View

Tarantini S, Valcarcel-Ares M, Yabluchanskiy A, Tucsek Z, Hertelendy P, Kiss T . Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype. J Gerontol A Biol Sci Med Sci. 2018; 73(7):853-863. PMC: 6001893. DOI: 10.1093/gerona/glx177. View

Vella C, Taylor K, Drummer D . High-intensity interval and moderate-intensity continuous training elicit similar enjoyment and adherence levels in overweight and obese adults. Eur J Sport Sci. 2017; 17(9):1203-1211. PMC: 6104631. DOI: 10.1080/17461391.2017.1359679. View

Craft S, Baker L, Montine T, Minoshima S, Watson G, Claxton A . Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2011; 69(1):29-38. PMC: 3260944. DOI: 10.1001/archneurol.2011.233. View

Carmody R, Gerber G, Luevano Jr J, Gatti D, Somes L, Svenson K . Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe. 2014; 17(1):72-84. PMC: 4297240. DOI: 10.1016/j.chom.2014.11.010. View

Banks W, Jaspan J, Huang W, Kastin A . Transport of insulin across the blood-brain barrier: saturability at euglycemic doses of insulin. Peptides. 1997; 18(9):1423-9. DOI: 10.1016/s0196-9781(97)00231-3. View

Marques-Iturria I, Pueyo R, Garolera M, Segura B, Junque C, Garcia-Garcia I . Frontal cortical thinning and subcortical volume reductions in early adulthood obesity. Psychiatry Res. 2013; 214(2):109-15. DOI: 10.1016/j.pscychresns.2013.06.004. View

Bullo M, Casas-Agustench P, Amigo-Correig P, Aranceta J, Salas-Salvado J . Inflammation, obesity and comorbidities: the role of diet. Public Health Nutr. 2007; 10(10A):1164-72. DOI: 10.1017/S1368980007000663. View

Mena M, Sacanella E, Vazquez-Agell M, Morales M, Fito M, Escoda R . Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet. Am J Clin Nutr. 2008; 89(1):248-56. DOI: 10.3945/ajcn.2008.26094. View

10.

McLean F, Grant C, Morris A, Horgan G, Polanski A, Allan K . Rapid and reversible impairment of episodic memory by a high-fat diet in mice. Sci Rep. 2018; 8(1):11976. PMC: 6086894. DOI: 10.1038/s41598-018-30265-4. View

11.

Hawkins B, Davis T . The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005; 57(2):173-85. DOI: 10.1124/pr.57.2.4. View

12.

Menezes da Costa R, Neves K, Mestriner F, Louzada-Junior P, Bruder-Nascimento T, Tostes R . TNF-α induces vascular insulin resistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice. Cardiovasc Diabetol. 2016; 15(1):119. PMC: 5000486. DOI: 10.1186/s12933-016-0443-0. View

13.

Kasper J, Milton A, Smith A, Laezza F, Taglialatela G, Hommel J . Cognitive deficits associated with a high-fat diet and insulin resistance are potentiated by overexpression of ecto-nucleotide pyrophosphatase phosphodiesterase-1. Int J Dev Neurosci. 2017; 64:48-53. PMC: 5893149. DOI: 10.1016/j.ijdevneu.2017.03.011. View

14.

Gorelick P, Scuteri A, Black S, DeCarli C, Greenberg S, Iadecola C . Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011; 42(9):2672-713. PMC: 3778669. DOI: 10.1161/STR.0b013e3182299496. View

15.

Tenorio T, Babu Balagopal P, Andersen L, Ritti-Dias R, Hill J, Lofrano-Prado M . Effect of Low- Versus High-Intensity Exercise Training on Biomarkers of Inflammation and Endothelial Dysfunction in Adolescents With Obesity: A 6-Month Randomized Exercise Intervention Study. Pediatr Exerc Sci. 2017; 30(1):96-105. DOI: 10.1123/pes.2017-0067. View

16.

Bender S, Herrick E, Lott N, Klabunde R . Diet-induced obesity and diabetes reduce coronary responses to nitric oxide due to reduced bioavailability in isolated mouse hearts. Diabetes Obes Metab. 2007; 9(5):688-96. DOI: 10.1111/j.1463-1326.2006.00650.x. View

17.

Vazquez L, Pazos F, Berrazueta J, Fernandez-Escalante C, Garcia-Unzueta M, Freijanes J . Effects of changes in body weight and insulin resistance on inflammation and endothelial function in morbid obesity after bariatric surgery. J Clin Endocrinol Metab. 2004; 90(1):316-22. DOI: 10.1210/jc.2003-032059. View

18.

Chen W, Balland E, Cowley M . Hypothalamic Insulin Resistance in Obesity: Effects on Glucose Homeostasis. Neuroendocrinology. 2017; 104(4):364-381. DOI: 10.1159/000455865. View

19.

Valls-Pedret C, Sala-Vila A, Serra-Mir M, Corella D, de la Torre R, Martinez-Gonzalez M . Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial. JAMA Intern Med. 2015; 175(7):1094-1103. DOI: 10.1001/jamainternmed.2015.1668. View

20.

Du H, van der A D, van Bakel M, van der Kallen C, Blaak E, van Greevenbroek M . Glycemic index and glycemic load in relation to food and nutrient intake and metabolic risk factors in a Dutch population. Am J Clin Nutr. 2008; 87(3):655-61. DOI: 10.1093/ajcn/87.3.655. View