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However, the key molecular mechanisms behind this disease have not been clarified. Methods: In this experiment, we fed zebrafish a high-fat diet (HFD) for 16 weeks to induce sarcopenic obesity. Results: After a dietary trial, HFD zebrafish exhibited an obese phenotype with skeletal muscle atrophy and decreased swimming capacity. We demonstrated that mitochondrial content and function were abnormal in SOB zebrafish skeletal muscle. These results may be associated with the impairment of mitophagy regulated by the PTEN-induced putative kinase 1 (PINK1)\/Parkin (PRKN) pathway. In addition, we also found that NOD-like receptor protein 3 (NLRP3)\/gasdermin D (GSDMD) signaling was activated with the upregulation of NLRP3, GSDMD-NT, and mature-IL1\u03b2, which indicated that pyroptosis was induced in SOB zebrafish skeletal muscle. Conclusions: Our study identified that impaired mitophagy and pyroptosis were associated with the pathogenesis of SOB. These results could potentially offer novel therapeutic objectives for the treatment of sarcopenic obesity.<\/jats:p>","DOI":"10.3390\/nu17101711","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T05:37:13Z","timestamp":1747633033000},"page":"1711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impaired Mitophagy Contributes to Pyroptosis in Sarcopenic Obesity Zebrafish Skeletal Muscle"],"prefix":"10.3390","volume":"17","author":[{"given":"Xiangbin","family":"Tang","sequence":"first","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyi","family":"Zou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0724-6989","authenticated-orcid":false,"given":"Zhanglin","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoqiong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1307-9785","authenticated-orcid":false,"given":"Xiyang","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changfa","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e13520","DOI":"10.1111\/obr.13520","article-title":"Obesity in South and Southeast Asia-A new consensus on care and management","volume":"24","author":"Tham","year":"2023","journal-title":"Obes. 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