---
title: "METTL3 and m6A Regulation of Triglyceride Metabolism Reduces Skeletal Muscle Atrophy in ALS"
id: "biorxiv-21-mettl3-mediated-m6a-modification-alleviates-skeletal-muscle-atrophy-in-als-by"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-21-mettl3-mediated-m6a-modification-alleviates-skeletal-muscle-atrophy-in-als-by"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.21.759261v1?rss=1"
published_at: "2026-10-24T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# METTL3 and m6A Regulation of Triglyceride Metabolism Reduces Skeletal Muscle Atrophy in ALS
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-21-mettl3-mediated-m6a-modification-alleviates-skeletal-muscle-atrophy-in-als-by
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.21.759261v1?rss=1)
- **Published At:** 2026-10-24T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study examined m6A RNA methylation in skeletal muscle from an hSOD1G93A transgenic mouse model of **ALS**, finding reduced global **m6A** levels and lower expression of the methyltransferase **METTL3**. - Multi-omics analysis linked m6A dysregulation to defective **triglyceride** metabolism in ALS muscle; the team reported altered metabolic signatures consistent with impaired lipid handling. - In vitro, investigators observed that **METTL3** promotes triglyceride accumulation in ALS myotubes through an m6A-dependent mechanism; overexpression improved cellular energy supply and reduced markers of muscle atrophy. - In vivo muscle-specific overexpression of Mettl3 reportedly attenuated atrophy, improved motor function, and extended survival in the ALS mouse model. - Mechanistic work identified **ACSL1** (fatty acid activation enzyme) as a downstream effector: **METTL3**-mediated m6A modification increased Acsl1 mRNA stability, leading to higher ACSL1 expression. - The m6A reader protein IGF2BP2 was required for the regulatory effect on Acsl1, indicating a writer-reader axis (METTL3–m6A–IGF2BP2) controlling ACSL1 and triglyceride metabolism. - The source did not report specific experimental doses, sample sizes, statistical values, or detailed methods for gene delivery and expression levels; those methodological specifics are absent from the provided abstract. - Authors reported no competing interests and declared funding sources from Chinese national and provincial science foundations and a local development plan; the article is a preprint and has not undergone peer review.
## Clinical Analysis & Structured Key Points
METTL3-mediated m6A modification alleviates skeletal muscle atrophy in ALS by regulating ACSL1-dependent triglyceride metabolism | bioRxiv Skip to main content New Results METTL3-mediated m6A modification alleviates skeletal muscle atrophy in ALS by regulating ACSL1-dependent triglyceride metabolism Qiupeng Yan , Lingyun Zhang , Xue Bai , Yingjun Guan , Haoyun Zhang , Jinmeng Liu , Baoxiang Zhuang , Mu Li , Xue Zhang , Xiaosu Chen , Xiaonan Ma , Chunjie Xu , Huilin Yang , Xin Huang , Fenghua Zhou , Yanchun Chen doi: https://doi.org/10.64898/2026.10.21.759261 Qiupeng Yan Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lingyun Zhang Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Xue Bai Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yingjun Guan Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Haoyun Zhang Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jinmeng Liu Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Baoxiang Zhuang Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mu Li Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Xue Zhang Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Xiaosu Chen Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Xiaonan Ma Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Chunjie Xu Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Huilin Yang Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Xin Huang Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Fenghua Zhou Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yanchun Chen Shandong second medical university Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: cyc7907{at}sdsmu.edu.cn Abstract Info/History Metrics Supplementary material Preview PDF Abstract Skeletal muscle-intrinsic defects are increasingly recognized as critical contributors to the pathogenesis of amyotrophic lateral sclerosis (ALS), yet the underlying molecular mechanisms remain poorly understood. N6-methyladenosine (m6A) is the most abundant post-transcriptional RNA modification in mammalian mRNAs that plays important regulatory roles in diverse physiological and pathological processes, however its role in ALS-associated skeletal muscle atrophy remains unknown. Here we found that global m6A methylation and the expression of its methyltransferase METTL3 are reduced in the skeletal muscle of hSOD1G93A transgenic ALS mice. Multi-omics analyses reveal that m6A dysregulation is closely associated with impaired triglyceride metabolism. Functionally, METTL3 promotes triglyceride accumulation in ALS skeletal muscle in an m6A-dependent manner; overexpression of METTL3 in ALS myotubes improves energy supply and alleviates muscle atrophy by promoting triglyceride accumulation. In vivo overexpression of Mettl3 in skeletal muscle attenuates muscle atrophy, improves motor performance, and prolongs survival of ALS mice. Mechanistically, we identify the fatty acid activation enzyme ACSL1 as a key downstream effector of METTL3-mediated regulation of triglyceride metabolism. METTL3-mediated m6A modification promotes the expression of Acsl1 by enhancing its mRNA stability. Further investigation revealed that the regulatory effect of m6A on Acsl1 expression depends on the m6A reader protein IGF2BP2. Collectively, our findings establish m6A modification as a critical regulator of skeletal muscle atrophy in ALS by maintaining triglyceride metabolic homeostasis, highlighting a promising therapeutic target for ALS. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared National Natural Science Foundation of China Shandong Provincial Natural Science Foundation , ZR2024QH628 , ZR2024MH112 Weifang Science and Technology Development Plan Project , 2024YX033 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted October 24, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Share METTL3-mediated m6A modification alleviates skeletal muscle atrophy in ALS by regulating ACSL1-dependent triglyceride metabolism Qiupeng Yan , Lingyun Zhang , Xue Bai , Yingjun Guan , Haoyun Zhang , Jinmeng Liu , Baoxiang Zhuang , Mu Li , Xue Zhang , Xiaosu Chen , Xiaonan Ma , Chunjie Xu , Huilin Yang , Xin Huang , Fenghua Zhou , Yanchun Chen bioRxiv 2026.10.21.759261; doi: https://doi.org/10.64898/2026.10.21.759261 Share This Article: Copy Citation Tools METTL3-mediated m6A modification alleviates skeletal muscle atrophy in ALS by regulating ACSL1-dependent triglyceride metabolism Qiupeng Yan , Lingyun Zhang , Xue Bai , Yingjun Guan , Haoyun Zhang , Jinmeng Liu , Baoxiang Zhuang , Mu Li , Xue Zhang , Xiaosu Chen , Xiaonan Ma , Chunjie Xu , Huilin Yang , Xin Huang , Fenghua Zhou , Yanchun Chen bioRxiv 2026.10.21.759261; doi: https://doi.org/10.64898/2026.10.21.759261 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8164) Biochemistry (19027) Bioengineering (15171) Bioinformatics (45344) Biophysics (22958) Cancer Biology (20115) Cell Biology (27308) Clinical Trials (138) Developmental Biology (14146) Ecology (21399) Epidemiology (2067) Evolutionary Biology (25810) Genetics (16343) Genomics (23840) Immunology (19025) Microbiology (43196) Molecular Biology (18345) Neuroscience (95071) Paleontology (713) Pathology (3033) Pharmacology and Toxicology (5200) Physiology (8281) Plant Biology (16271) Scientific Communication and Education (2116) Synthetic Biology (4646) Systems Biology (10386) Zoology (2427)
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