Antihypertensive agents do not prevent blood–brain barrier dysfunction and cognitive deficits in dietary-induced obese mice

• Published in: International Journal of Obesity 2017-06, Vol.41 (6), p.926-934
• Main Authors: Mamo, J C L, Lam, V, Giles, C, Coulson, S H, Fimognari, N, Mooranian, A, Al-Salami, H, Takechi, R
• Format: Article
• Language: English
• Subjects: 14/19; 631/378/2649/2150; 631/443/319/1642/393; 631/443/592/75; 64/60; 692/308/2778; 692/499; 82/51; 96/31; Alzheimer's disease; Animals; Antihypertensive agents; Antihypertensive Agents - pharmacology; Antihypertensives; Blood pressure; Blood-brain barrier; Blood-Brain Barrier - drug effects; Body weight; Care and treatment; Cognition Disorders - blood; Cognition Disorders - physiopathology; Cognitive ability; Cognitive disorders; Complications and side effects; Dementia; Dementia disorders; Development and progression; Diet; Diet, High-Fat - adverse effects; Disease Models, Animal; Disruption; Epidemiology; Health Promotion and Disease Prevention; Health sciences; High fat diet; Hypertension; Hypertension - blood; Hypertension - drug therapy; Hypertension - physiopathology; Insulin; Internal Medicine; Low fat diet; Male; Medicine; Medicine & Public Health; Membrane permeability; Metabolic Diseases; Metabolic syndrome; Mice; Mice, Obese; Neurodegeneration; Obesity; Obesity - blood; Obesity - drug therapy; Obesity - physiopathology; Oils & fats; original-article; Permeability; Physiological aspects; Public Health; Risk analysis; Risk factors; Ursodeoxycholic acid
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2017.57

Background: While vascular risk factors including Western-styled diet and obesity are reported to induce cognitive decline and increase dementia risk, recent reports consistently suggest that compromised integrity of cerebrovascular blood–brain barrier (BBB) may have an important role in neurodegeneration and cognitive deficits. A number of studies report that elevated blood pressure increases the permeability of BBB. Methods: In this study, we investigated the effects of antihypertensive agents, candesartan or ursodeoxycholic acid (UDCA), on BBB dysfunction and cognitive decline in wild-type mice maintained on high fat and fructose (HFF) diet for 24 weeks. Results: In HFF-fed mice, significantly increased body weight with elevated blood pressure, plasma insulin and glucose compared with mice fed with low-fat control chow was observed. Concomitantly, significant disruption of BBB and cognitive decline were evident in the HFF-fed obese mice. Hypertension was completely prevented by the coprovision of candesartan or UDCA in mice maintained on HFF diet, while only candesartan significantly reduced the body weight compared with HFF-fed mice. Nevertheless, BBB dysfunction and cognitive decline remained unaffected by candesartan or UDCA. Conclusions: These data conclusively indicate that modulation of blood pressure and/or body weight may not be directly associated with BBB dysfunction and cognitive deficits in Western diet-induced obese mice, and hence antihypertensive agents may not be effective in preventing BBB disruption and cognitive decline. The findings may provide important mechanistical insights to obesity-associated cognitive decline and its therapy.