Your new experience awaits. Try the new design now and help us make it even better

ORIGINAL RESEARCH article

Front. Aging Neurosci.

Sec. Neuroinflammation and Neuropathy

Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1644988

Western Diet-induced Visceral Adipose Tissue Inflammation Promotes Alzheimer's Disease Pathology via Microglial Activation in a Mouse Model

Provisionally accepted
Ji Sun LimJi Sun Lim1Soyoung KwakSoyoung Kwak1Mi-Hee YuMi-Hee Yu1Mee-Na ParkMee-Na Park2Hye Suk BaekHye Suk Baek2Junho KangJunho Kang3Jeongho HongJeongho Hong1Jin Kyung KimJin Kyung Kim1Hye Won LeeHye Won Lee1Sang-Woo LeeSang-Woo Lee4Shin KimShin Kim2*Hae Won KimHae Won Kim1*
  • 1Keimyung University Daegu Dongsan Hospital, Daegu, Republic of Korea
  • 2Keimyung University School of Medicine, Daegu, Republic of Korea
  • 3Keimyung University Dongsan Medical Center, Daegu, Republic of Korea
  • 4Kyungpook National University School of Medicine, Daegu, Republic of Korea

The final, formatted version of the article will be published soon.

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

Western diet (WD)-induced visceral adipose tissue (VAT) inflammation is characterized by adipocyte hypertrophy, hypoxia, and apoptosis. Epididymal white adipose tissue (eWAT), a representative VAT depot in rodents, plays a central role in WD-induced inflammation by secreting pro-inflammatory cytokines that contribute to systemic and neuroinflammation. However, the mechanistic link between WD-driven eWAT inflammation and Alzheimer's disease (AD) pathology remains unclear. In this study, WD-fed mice exhibited significantly increased levels of neuroinflammatory markers and increased hippocampal levels of AD-related proteins including amyloid-beta oligomers, amyloid precursor protein, and phosphorylated tau. Additionally, F-18 fluorodeoxyglucose PET imaging revealed reduced glucose metabolism in the thalamus and hippocampus of WD-fed mice compared to controls. RNA sequencing of eWAT and cytokine profiling of plasma identified CCL8, CCL9, CXCL13, and IL-18 as significantly elevated proinflammatory cytokines. In vitro analyses demonstrated that these eWAT-associated cytokines directly activate microglial cells via the IL-6/STAT3 signaling pathway, promoting hippocampal neuronal cell death. Collectively, these findings elucidate a critical pathway through which WDinduced eWAT inflammation exacerbates AD pathology through a systemic-to-neuroinflammation axis, highlighting the therapeutic potential of targeting eWAT-associated cytokines to mitigate dietassociated AD progression.

Keywords: western diet, visceral adipose tissue, Alzheimer's disease, Pro-inflammatory cytokines, cognitive impairment

Received: 11 Jun 2025; Accepted: 21 Aug 2025.

Copyright: © 2025 Lim, Kwak, Yu, Park, Baek, Kang, Hong, Kim, Lee, Lee, Kim and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Shin Kim, Keimyung University School of Medicine, Daegu, Republic of Korea
Hae Won Kim, Keimyung University Daegu Dongsan Hospital, Daegu, Republic of Korea

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material