Research Paper Volume 13, Issue 19 pp 23133—23148

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

Chao-Jin Xu1, *, , Mei-Qi Li2, *, , Li-Zhao2, , Wei-Guang Chen1, , Jun-Ling Wang3, ,

  • 1 Department of Histology and Embryology, School of Basic Medical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China
  • 2 School of 2nd Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China
  • 3 Center for Reproductive Medicine, Affiliated Hospital 1 of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China
* Equal contribution

Received: July 19, 2021       Accepted: September 7, 2021       Published: October 7, 2021
How to Cite

Copyright: © 2021 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


HFD: High-fat diet; GFAP: Glial fibrillary acidic protein; Iba-1: ionized calcium binding adaptor molecule 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; BACE1: beta-site APP-cleaving enzyme 1; MAPK: mitogen-activated protein kinase, APP: amyloid-beta precursor protein; IF: Immunofluorescence; BBB: blood–brain barrier; Iba-1: ionized calcium binding adapter protein 1.