ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition, Psychology and Brain Health
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1585640
This article is part of the Research TopicBeyond the Plate: The Role of Diet and the Microbiota-Gut-Brain Axis in Neurodegenerative DiseasesView all articles
Coconut oil derived medium-chain triglycerides ameliorated memory deficits via promoting neurite outgrowth and maintaining gut homeostasis in 5×FAD mice
Provisionally accepted
- Guangdong Ocean University, Zhanjiang, China
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
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by neurite atrophy, neuronal loss, and memory impairment. Medium-chain triglycerides (MCT), a type of fatty acid predominantly found in coconut oil, have been shown to improve metabolic syndrome as well as cognitive performance via ketone production in humans. Here, we investigated the protective effects of MCT on neurite atrophy and memory deficits in 5×FAD mice and elucidated the underlying mechanisms. First, virgin coconut oil (VCO), refined, bleached, and deodorized coconut oil (RBDCO), and MCT were orally administered to 6-8 months old 5×FAD mice for 9 consecutive weeks, the effects on cognition were then evaluated. MCT demonstrated superior effects compared to RBDCO and VCO in reducing Aβ levels, inhibiting hyperactivated microglia and astroglia, protecting neurons, and mitigating memory decline. Further, metagenomic analysis and RT-qPCR results revealed that MCT intervention increased the relative abundance of Akkermansia, reduced intestinal permeability, and elevated the concentration of short-chain fatty acids in the brain.Additionally, MCT treatment significantly protected primary cortical neurons against Aβ25-35induced apoptosis and promoted neurite regeneration. Transcriptome and RT-qPCR data suggested that Ucp1 and Flor1 may be potential targets through which MCT exerts its neuroprotective effects.Our findings suggest that MCT may help prevent the progression of AD by promoting neurite outgrowth and maintaining gut homeostasis in 5×FAD mice, offering a theoretical foundation for the development of dietary therapies for AD.
Keywords: medium-chain triglycerides, 5×FAD mice, Neurite regeneration, Alzheimer's disease, Gut homeostasis
Received: 01 Mar 2025; Accepted: 20 May 2025.
Copyright: © 2025 Chen, Li, Jiang, Zhou, Zhao, Zhang, Xia and Yang. 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: Zhiyou Yang, Guangdong Ocean University, Zhanjiang, China
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.