Visceral adiposity links cerebrovascular dysfunction to cognitive impairment in middle-aged mice

Pétrault, Olivier; Pétrault, Maud; Ouk, Thavarak; Bordet, Régis; Bérézowski, Vincent; Bastide, Michèle

doi:10.1016/j.nbd.2019.104536

Cited by 20 publications

(22 citation statements)

References 48 publications

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“…31,33 Clinically, visceral fat is associated with a higher prevalence of white matter lesions and small lacunar infarcts, indicators of small vessel disease. 34,35 Visceral adiposity has also been linked to cerebrovascular dysfunction and cognitive impairment in male mice 31 ; however, direct comparisons with females are rare. Our novel sex-specific correlations between visceral fat and specific memory tasks (episodic memory in males, spatial memory in females) could be due to sex differences in systemic inflammation induced by the visceral fat.…”

Section: Discussionmentioning

confidence: 99%

Sex‐specific effects of high‐fat diet on cognitive impairment in a mouse model of VCID

et al. 2020

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Half of all dementia patients have evidence of vascular contributions to cognitive impairment and dementia (VCID), either as a single pathology or as a multi-etiology dementia, 1 yet, there remains a severe lack of knowledge regarding VCID. Type 2 diabetes is a major risk factor for VCID, as it is known to cause damage to the cerebral vasculature and blood brain barrier (BBB). 2-4 Furthermore, there is a sex difference in risk for VCID that varies by metabolic status. While most studies agree that in a nondiabetic population, VCID risk is slightly higher in men than in women (under the age of 90), 5 in a pooled analysis of 2.3 million individuals, it was found

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Section: Discussionmentioning

confidence: 99%

Sex‐specific effects of high‐fat diet on cognitive impairment in a mouse model of VCID

et al. 2020

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“…On the contrary, middle‐aged obese mice showed increased density of the pial and parenchymal arteriolar compartment compared with young‐adult obese mice, which could potentially compensate for the decrease of capillaries with aging that we observed in middle‐aged versus young‐adult control mice. This counterintuitive protective effect has to be discussed in light of controversial data published about the density of capillaries under a HFD: on one hand, a HFD (15) and aging (38) have been shown to have a detrimental effect on capillary density, but on the other hand, the endothelial network has been shown to remain stable in the hippocampus of long‐term HFD‐fed rats (39) or mice (13). The use of different vascular quantitation techniques as well as the quality and duration of HFD can be causal in these discrepancies.…”

Section: Discussionmentioning

confidence: 99%

“…OBESITY BIOLOGY AND INTEGRATED PHYSIOLOGY on capillary density, but on the other hand, the endothelial network has been shown to remain stable in the hippocampus of long-term HFDfed rats (39) or mice (13). The use of different vascular quantitation techniques as well as the quality and duration of HFD can be causal in these discrepancies.…”

Section: Original Articlementioning

confidence: 99%

Obesity in Midlife Hampers Resting and Sensory‐Evoked Cerebral Blood Flow in Mice

Soleimanzad

Montaner

Ternier

et al. 2020

Obesity

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This study aimed to investigate the effects of a high-fat diet (HFD) and aging on resting and activity-dependent cerebral blood flow (CBF). Methods: To run a comparison between obese and age-matched control animals, 6-week-old mice were fed either with regular chow or an HFD for 3 months or 8 months. Glucose tolerance and insulin sensitivity were assessed for metabolic phenotyping. Resting and odor-evoked CBF at the microvascular scale in the olfactory bulb (OB) was investigated by multiexposure speckle imaging. Immunolabeling-enabled imaging of solvent-cleared organs was used to analyze vascular density. The ejection fraction was studied by using cardioechography. Olfactory sensitivity was tested by using a buried-food test. Results: Glucose intolerance and compromised odor-evoked CBF were observed in obese mice in the younger group. Prolonged HFD feeding triggered insulin resistance and stronger impairment in activity-dependent CBF. Aging had a specific negative impact on resting CBF. There was no decrease in vascular density in the OB of obese mice, although cardiac function was impaired at both ages. In addition, decreased olfactory sensitivity was observed only in the older, middle-aged obese mice. Conclusions: OB microvasculature in obese mice showed a specific functional feature characterized by impaired sensory-evoked CBF and a specific deleterious effect of aging on resting CBF.

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“…Such alterations are likely to impact brain perfusion and to limit nutrient delivery for fueling neuronal energetics (Glaser et al, 2012;Bangen et al, 2018). In mice, exposure to HFD impairs vascular reactivity (relaxation and contractile responses) and cerebral blood flow of the middle cerebral artery and of intraparenchymal micro vessels in prefrontal cortex and hippocampus, without changes of baseline perfusion (Pétrault et al, 2019). Accordingly, HFD feeding also exacerbates memory impairment induced by carotid occlusion without changes in basal cerebral blood flow (Zuloaga et al, 2016).…”

Section: Hyperglycemia and Brain Glucose Toxicitymentioning

confidence: 99%

Brain Metabolism Alterations in Type 2 Diabetes: What Did We Learn From Diet-Induced Diabetes Models?

García-Serrano

Duarte

2020

Front. Neurosci.

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Type 2 diabetes (T2D) is a metabolic disease with impact on brain function through mechanisms that include glucose toxicity, vascular damage and blood-brain barrier (BBB) impairments, mitochondrial dysfunction, oxidative stress, brain insulin resistance, synaptic failure, neuroinflammation, and gliosis. Rodent models have been developed for investigating T2D, and have contributed to our understanding of mechanisms involved in T2D-induced brain dysfunction. Namely, mice or rats exposed to diabetogenic diets that are rich in fat and/or sugar have been widely used since they develop memory impairment, especially in tasks that depend on hippocampal processing. Here we summarize main findings on brain energy metabolism alterations underlying dysfunction of neuronal and glial cells promoted by diet-induced metabolic syndrome that progresses to a T2D phenotype.

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Visceral adiposity links cerebrovascular dysfunction to cognitive impairment in middle-aged mice

Cited by 20 publications

References 48 publications

Sex‐specific effects of high‐fat diet on cognitive impairment in a mouse model of VCID

Sex‐specific effects of high‐fat diet on cognitive impairment in a mouse model of VCID

Obesity in Midlife Hampers Resting and Sensory‐Evoked Cerebral Blood Flow in Mice

Brain Metabolism Alterations in Type 2 Diabetes: What Did We Learn From Diet-Induced Diabetes Models?

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