{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:48:43Z","timestamp":1782272923622,"version":"3.54.5"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Exercise-induced regulation of cortical GPCR pathways in diabetic obesity remains unclear. This study aimed to investigate exercise-associated GPCR-related transcriptomic pathway changes in the cerebral cortex of diabetic-obese rats. Cerebral cortical samples from male Zucker Fatty Diabetes Mellitus (ZFDM) rats subjected to a 12-week swimming program were examined using RNA sequencing, functional enrichment, GSOAP clustering, and STRING-based protein\u2013protein interaction (PPI) analysis. Exercise training reduced fasting glucose and body weight. RNA sequencing identified 817 exercise-responsive transcripts (403 upregulated and 414 downregulated; p &lt; 0.05), including 48 associated with GPCR signaling. Results showed that these 48 genes mapped to three major GPCR-related networks: cAMP signaling, with increased Adcyap1r1, Gipr, Tshr, and Vipr2 and decreased Vip, Chrm1, Gabbr2, and Sst; calcium signaling, with increased Ntsr1 and Trhr and decreased Chrm1; and neuroactive ligand\u2013receptor interaction, with increased Trh, Trhr, and Crh and decreased Opr-related transcripts. These findings provide hypothesis-generating evidence for interpreting cortical GPCR-related transcriptomic pathway associations in diabetic-obese conditions.<\/jats:p>","DOI":"10.3390\/ijms27125602","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exercise Training Regulates Cortical GPCR-Mediated Signaling Networks Through cAMP, Calcium, and Neuroactive Ligand\u2013Receptor Interaction Pathways in Diabetic\u2013Obese Rats: An In Silico Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7246-4822","authenticated-orcid":false,"given":"Yin-Yu","family":"Chiang","sequence":"first","affiliation":[{"name":"PhD Program for Health Science and Industry, China Medical University, Taichung 406040, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3703-6544","authenticated-orcid":false,"given":"Michael Anekson","family":"Widjaya","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8393-8349","authenticated-orcid":false,"given":"Shin-Da","family":"Lee","sequence":"additional","affiliation":[{"name":"PhD Program in Healthcare Science, Department of Physical Therapy, China Medical University, Taichung 406040, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e14974","DOI":"10.1111\/dme.14974","article-title":"Quantification of changes in human islet G protein-coupled receptor mRNA expression in obesity","volume":"39","author":"Lyu","year":"2022","journal-title":"Diabet. 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