Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood–Brain Barrier Permeability and Neuroinflammation as Triggering Events

Abstract

Graphical AbstractAn illustrative scheme summarizing the main outcomes in Swiss mice fed high-fat diet (HFD), with their exact time of onset of changes in the hippocampus. An increase in the expression of proinflammatory cytokines, together with the permeability of the blood–brain barrier was detected after 2 days of HFD. Even in the first week of dietary intervention, memory and learning impairment, depressive-like behavior, and synaptic changes were observed at 3, 5, and 7 days, respectively. Later hippocampal alterations (after 4 weeks of HFD consumption) include mitochondrial dysfunction and astrocytic activation.

Early exposure to high-fat diet impairs central and peripheral metabolic function: Impacts on cognition and mitochondrial function

“…Yang and colleagues observed that the excess of lipid intake from diet diminishes mitochondrial biogenesis and alters fusion- fission protein levels in hippocampus of mice (Yang et al, 2021). We also verified a reduced hippocampal mitochondrial function in adult mice fed a HFD (de Paula et al, 2021). Furthermore, BAT mitochondrial metabolism has currently gathered attention as a therapeutic target for obesity and related metabolic disorders (Lettieri Barbato et al, 2015; Tseng et al, 2010).…”

“…A recent study from our group reported memory dysfunction in adult Swiss mice as early as 3 days after HFD introduction (de Paula et al, 2021). Interestingly, some studies emphasize that behavior and metabolic changes are more intense when HFD is introduced earlier in life.…”

Neurovascular Dysfunction in Diverse Communities With Health Disparities—Contributions to Dementia and Alzheimer’s Disease

“…It has previously been shown that energy-dense food consumption triggers severe health conditions such as metabolic syndrome, cardiovascular disorder, neurovascular dysfunction, memory deficits, as well as AD ( Thériault et al, 2016 ; Ting et al, 2017 ; Moreno-Fernández et al, 2018 ; Lasker et al, 2019 ; Bracko et al, 2020 ). Studies in animals fed with short-term or long-term enriched-energy diet increased the permeability of the BBB as demonstrated by an elevation of extravascular immunoglobulin G deposits and albumin content in the hippocampus ( de Aquino et al, 2018 ; Yamamoto et al, 2019 ; de Paula et al, 2021 ). Animals fed with a high-calorie diet exhibited attenuation of tight junction proteins claudin 5 and occludin, alleviation of collagen type IV, augmented fenestration of endothelial cells, and astrogliosis ( de Aquino et al, 2018 ; Yamamoto et al, 2019 ).…”

“…Additionally, Alabamians with less education ( Figure 2A ) and low income ( Figure 2B ) were more susceptible to diabetes ( Explore Diabetes in Alabama, 2021 Annual Report). Several studies have shown an association between diet-induced obesity or diabetes with vascular dysfunction ( Chang et al, 2014 ; de Paula et al, 2021 ; Li et al, 2021 ). Excessive caloric consumption stimulates peripheral immune cells, induces the generation of proinflammatory cytokines and increases oxidative stress, which have all been linked to BBB dysfunction ( Salameh et al, 2019 ).…”

“…BBB breakdown was also found in a streptozotocin-induced diabetes model that had reduced levels of tight junction proteins (e.g., occludin, and zonula occludens-1), and increased protein levels of cell adhesion molecules (e.g., intercellular adhesion molecule 1, and vascular adhesion protein 1) ( Aggarwal et al, 2018 ). Importantly, BBB leakage leads to the activation of glial cells, resulting in the release of proinflammatory cytokines in the brain, causing neuroinflammation and cognitive decline ( de Aquino et al, 2018 ; Salameh et al, 2019 ; de Paula et al, 2021 ). Notably, a large amount of Aβ accumulation was detected in the brain of a high-fat diet-induced obese model ( Busquets et al, 2017 ).…”