{
  "abstract": "Purpose: This study aimed to investigate the protective effects and potential mechanisms of exercise against long-term high-fat diet (HFD)-induced skeletal muscle dysfunction, with a focus on ADP-ribosylation factor 1 (ARF1)-related autophagy–lysosome markers and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Methods: Forty male C57BL/6 mice were randomly divided into a normal diet group (DC) and an HFD group, and the latter was further subdivided into a model group (MG), exercise group (EG), Nrf2 inhibitor group (NG), and exercise combined with Nrf2 inhibitor group (ENG) after 12 weeks of HFD feeding. EG received 6 weeks of moderate-intensity treadmill exercise, NG was treated with Nrf2 inhibitor for 6 weeks, and ENG received both the 6-week treadmill exercise and inhibitor injections simultaneously. Serum lipid, blood glucose and insulin resistance indices were detected; skeletal muscle morphology was observed by H&E staining; mRNA and protein expression of ARF1, ULK1, ATP6V0A1 and other factors were determined by RT-qPCR, Western blotting and immunohistochemistry; the oxidative stress index was measured by an ELISA; and the colocalization of ARF1/ATP6V0A1 with the lysosomal marker Lamp1 was analyzed by immunofluorescence. Results: Long-term HFD significantly increased mouse body weight, serum TC, TG, LDL-C, FBG levels and the HOMA-IR index, induced morphological alterations in skeletal muscle (loose myofiber arrangement, abundant intracellular vacuoles), inhibited the mRNA expression of ARF1, ULK1 and ATP6V0A1, and elevated malondialdehyde (MDA) content (p < 0.05 or p < 0.01). Six weeks of moderate-intensity treadmill exercise effectively improved HFD-induced metabolic disorders and skeletal muscle morphological damage, upregulated the expression of ARF1, ULK1 and ATP6V0A1, and reduced oxidative stress (p < 0.05 or p < 0.01). Notably, luteolin-mediated inhibition of Nrf2 signaling may partially reverse exercise-induced alterations in ARF1-related autophagy–lysosome markers and skeletal muscle morphology. Conclusions: Long-term HFD may induce morphological alterations in skeletal muscle, accompanied by changes in ARF1-associated autophagy–lysosome markers and elevated oxidative stress. Conversely, moderate-intensity exercise may ameliorate HFD-related changes in skeletal muscle morphology, potentially via Nrf2 signaling, providing a potential molecular target and theoretical basis for the exercise intervention strategies against HFD-induced metabolic-related skeletal muscle dysfunction.",
  "abstract_shown": true,
  "affiliations": [
    "School of Education and Physical Education, Yangtze University, Jingzhou 434023, China",
    "Department of Biochemistry and Molecular Biology, Center for Molecular Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shujuan Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuan Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Ruohan Xia"
    },
    {
      "affs": [
        1
      ],
      "name": "Xianwang Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c02fars45926v.bib",
  "cited_by": 0,
  "doi": "10.3390/nu18203329",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13708183/?tool=EBI",
  "id": "c02fars45926v",
  "issns": [
    "2072-6643"
  ],
  "landing_url": "https://www.mdpi.com/2072-6643/18/20/3329",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7221521987",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13708183/pdf/?tool=EBI",
  "pmcid": "PMC13708183",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/c02fars45926v.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:56Z",
      "native_id": "10.3390/nu18203329",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6643/18/20/3329"
    },
    {
      "first_seen": "2026-10-30T12:21:25Z",
      "native_id": "PMC:PMC13708183",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13708183"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Autophagy in Disease and Therapy",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Exercise Is Associated with Skeletal Muscle Autophagy–Lysosome-Related Markers and Nrf2/ARF1 Signaling in HFD Mice",
  "title_text": "Exercise Is Associated with Skeletal Muscle Autophagy–Lysosome-Related Markers and Nrf2/ARF1 Signaling in HFD Mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:25Z",
  "url": "https://research.draconitic.com/paper/c02fars45926v",
  "venue": "Nutrients",
  "versions": []
}