The Effect of High Fat Diet on Cerebrovascular Health and Pathology: A Species Comparative Review

Abstract

In both humans and animal models, consumption of a high-saturated-fat diet has been linked to vascular dysfunction and cognitive impairments. Laboratory animals provide excellent models for more invasive high-fat-diet-related research. However, the physiological differences between humans and common animal models in terms of how they react metabolically to high-fat diets need to be considered. Here, we review the factors that may affect the translatability of mechanistic research in animal models, paying special attention to the effects of a high-fat diet on vascular outcomes. We draw attention to the dissociation between metabolic syndrome and dyslipidemia in rodents, unlike the state in humans, where the two commonly occur. We also discuss the differential vulnerability between species to the metabolic and vascular effects of macronutrients in the diet. Findings from animal studies are better interpreted as modeling specific aspects of dysfunction. We conclude that the differences between species provide an opportunity to explore why some species are protected from the detrimental aspects of high-fat-diet-induced dysfunction, and to translate these findings into benefits for human health.

Xanthohumol improves cognition in farnesoid X receptor-deficient mice on a high-fat diet

“…The authors later showed that a diet containing as little as 20% saturated fatty acid (SFA) content was enough to impair cognition in young rodents ( Greenwood and Winocur, 2005 ). Since those initial studies, a large body of work, including work from our group, has confirmed the finding that an HFD can impair cognition, in both rodents and humans ( Freeman et al, 2013 ; Johnson et al, 2016 ; Kalmijn, 2000 ; Miranda et al, 2018 ; Smith et al, 2011 ; Winocur and Greenwood, 2005 ; Zimmerman et al, 2021 ).…”

The Link between Gut Dysbiosis Caused by a High-Fat Diet and Hearing Loss

“…In contrast, in a eubiotic state, the BLB protects the cochlea from pathogens, which would otherwise compromise cochlear integrity, causing inflammation and injury. This can be postulated based on evidence that the BBB [189][190][191] and the BLB [192,193] increase their permeability in response to the increased presence of the bacterial metabolite LPS.…”

Amelioration of cognitive impairment using epigallocatechin-3-gallate in ovariectomized mice fed a high-fat diet involves remodeling with Prevotella and Bifidobacteriales

“…However, not all postmenopausal women are susceptible to neurological disease ( Tamaria et al, 2013 ). A high-fat diet (HFD) is considered a risk factor for multiple diseases, such as gastrointestinal cancer ( Tong et al, 2021 ), cerebrovascular disease ( Zimmerman et al, 2021 ), and AD ( Barnes and Yaffe, 2011 ), as well as for postmenopausal women ( Naworska and Bak-Sosnowska, 2019 ). A previous study demonstrated that an HFD accelerated cognitive decline in estrogen-deficient rats by aggravating mitochondrial and synaptic dysfunction (Pratchayasakul et al, 2015).…”