Short-term high-fat diet favors the appearances of apoptosis and gliosis by activation of ERK1/2/p38MAPK pathways in brain

Abstract

High-fat diet (HFD) has been associated with neuroinflammation and apoptosis in distinct brain regions. To explore the effect of short-term (7, 14 and 21 days) high-fat overfeeding on apoptosis, inflammatory signaling proteins, APP changes and glial cell activities in cerebral cortex and cerebellum. Mice were fed with HFD for different lengths (up to 21 days) and after each time body weights of mice was tested, then the apoptotic proteins, IL-1β, APP, BACE1and MAPKs, Akt and NF-κB signaling activity were evaluated by western blots. Results demonstrate that short period of high-fat overnutrition significantly promotes apoptosis, APP expression at day 21 of cerebral cortex and at day 7 of cerebellum compared to chow diet. In addition, increased GFAP + astrocytes, Iba-1 + microglia and IL-1β 30 were observed in cerebral cortex after 21 days HFD, but no changes for 7 days overfeeding of cerebellum. Serendipitously, ERK1/2 pathway was activated both in cerebral cortex and cerebellum for different time course of HFD. Furthermore, increased phospho-p38 MAPK level was observed in cerebellum only. In consistent with in vivo results, SH-SY5Y cells treatment with cholesterol (50 μM, 100 μM) for 48 h culture in vitro demonstrated that pro-apoptotic proteins were enhanced as well. In brief, short-term HFD consumption increases sensitivity to apoptosis, APP and IL-1β production as well as gliosis in cerebral cortex and cerebellum, which may be related to enhancement of ERK1/2 and p38 MAPK activation.

Short-term high-fat diet alters the mouse brain magnetic resonance imaging parameters consistently with neuroinflammation on males and metabolic rearrangements on females. A pre-clinical study with an optimized selection of linear mixed-effects models

“…On males, the significant MTR increases during HFD, detected in all areas, and in the hippocampus as early as 7 days after diet diversification, are consistent with increases in macromolecule-bound water content. These results are in agreement with the augmented presence of astrocytes and microglia that occur during HFD-induced cerebral inflammation ( Thaler et al, 2012 ; Xu et al, 2021 ). On females, on the contrary, neither diet nor any of its corresponding time or area interactions revealed altered MTR.…”

Immunohistochemical analysis of caspase expression in the brains of individuals with obesity or overweight

“…In the present study, the apoptotic activity of brain tissue from donors with obesity was evaluated by immunohistochemistry. The mechanisms underlying the damage and therefore neuronal death in obesity are still unknown, but the evidence suggests that chronic systemic humoral inflammation may be associated with a reduced volume of gray matter 26,27 . Thus, the aim of this study was to compare the expression of caspases in the brains of donors with obesity or overweight and normal weight.…”

“…These structural changes in the brains of individuals with obesity could be associated with lower neuronal density 22 and are probably derived from neuroinflammation that induces apoptosis mechanisms. Animal model studies have shown that high‐fat diet and diet‐induced obesity are associated with neuroinflammation and apoptosis in central nervous system 23–27 …”

“…Animal model studies have shown that high‐fat diet and diet‐induced obesity are associated with neuroinflammation and apoptosis in central nervous system. 23 , 24 , 25 , 26 , 27 …”

“…Animal model studies have shown that high-fat diet and diet-induced obesity are associated with neuroinflammation and apoptosis in central nervous system. [23][24][25][26][27] In the present study, the apoptotic activity of brain tissue from donors with obesity was evaluated by immunohistochemistry. The mechanisms underlying the damage and therefore neuronal death in obesity are still unknown, but the evidence suggests that chronic systemic humoral inflammation may be associated with a reduced volume of gray matter.…”