{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:12:11Z","timestamp":1790165531405,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alabama Agricultural Experimental Station (AAES), the Hatch\/Multistate Funding program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Skeletal muscle plays a critical role in metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). Muscle atrophy, characterized by a decrease in muscle mass and function, occurs due to an imbalance between the rates of muscle protein synthesis and degradation. This study aimed to investigate the molecular mechanisms that lead to muscle atrophy in obese and T2DM mouse models. Additionally, the effect of nerve growth factor (NGF) on the protein synthesis and degradation pathways was examined. Male mice were divided into three groups: a control group that was fed a standard chow diet, and two experimental groups that were fed a Western diet. After 8 weeks, the diabetic group was injected with streptozotocin to induce T2DM. Each group was then further divided into NGF-treated or non-treated control group. In the gastrocnemius muscles of the Western diet group, increased expressions of myostatin, autophagy markers, and ubiquitin ligases were observed. Skeletal muscle tissue morphology indicated signs of muscle atrophy in both obese and diabetic mice. The NGF-treated group showed a prominent decrease in the protein levels of myostatin and autophagy markers. Furthermore, the NGF-treated group showed an increased Cyclin D1 level. Western diet-induced obesity and T2DM may be linked to muscle atrophy through upregulation of myostatin and subsequent increase in the ubiquitin and autophagy systems. Moreover, NGF treatment may improve muscle protein synthesis and cell cycling.<\/jats:p>","DOI":"10.3390\/ijms25084307","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T10:24:26Z","timestamp":1713176666000},"page":"4307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Targeting Molecular Mechanisms of Obesity- and Type 2 Diabetes Mellitus-Induced Skeletal Muscle Atrophy with Nerve Growth Factor"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1341-8831","authenticated-orcid":false,"given":"Lauren","family":"Jun","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Wen","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5882-6994","authenticated-orcid":false,"given":"Megan","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Jafari","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8124-9710","authenticated-orcid":false,"given":"Emily","family":"Knight","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-0012","authenticated-orcid":false,"given":"Thangiah","family":"Geetha","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"},{"name":"Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6443-8269","authenticated-orcid":false,"given":"Michael W.","family":"Greene","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"},{"name":"Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeganathan Ramesh","family":"Babu","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"},{"name":"Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"ref_1","unstructured":"World Obesity Atlas 2023 (2024, February 21). 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