{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T10:21:59Z","timestamp":1783506119238,"version":"3.55.0"},"reference-count":46,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:p>The pancreas suffers from lipotoxicity, which threatens the survival of pancreatic islets. Dual peroxisome proliferator-activated receptor-alpha\/gamma (PPAR-\u03b1\/\u03b3) agonism is a promising method for treating type 2 diabetes mellitus (T2DM). This study evaluated the effects of single PPAR-\u03b1 and PPAR-\u03b3 or their combined activation on pancreatic islet remodelling, beta cell proliferation, identity and maintenance in an experimental obesity model. Fifty three-month-old mice, randomly divided to receive the control (C) or high-fat (HF) diet for ten weeks, were then redivided for a four-week treatment: C, HF, HF-a (received the PPAR-\u03b1 agonist), HF-g (received the PPAR-\u03b3 agonist pioglitazone) and HF-d (received PPAR-\u03b1\/\u03b3 agonists). The HF group was overweight, had oral glucose intolerance, showed a proinflammatory adipokine profile, exhibited increased alpha and beta cell masses and showed islet gene expression compatible with compromised beta cell proliferation and favoured dedifferentiation. All treatments reduced body weight, mitigated oral glucose intolerance and produced an anti-inflammatory adipokine profile, which rescued islet cytoarchitecture and beta cell function. Principal component analysis (PCA) revealed a shift in the antiapoptotic gene Bcl2 and beta cell proliferation genes (Pax4 and Neurog3) in HF-a. Conversely, HF-g and HF-d benefited from the upregulation of genes related to beta cell function (Fgf21, Glut2 and Glp1r), identity and maintenance (Pdx1, Neurod1, Mafa and Nkx6.1). The HF mice were glucose intolerant, showing islet hypertrophy and low beta cell identity-related genes. In contrast, PPAR activation rescued islet structure, and PCA showed that the PPAR-\u03b1\/\u03b3 combination was the most effective treatment because it favoured beta cell function, identity and maintenance-related genes, halting the T2DM spectrum in diet-induced obese mice.<\/jats:p>","DOI":"10.1530\/joe-24-0180","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T14:56:52Z","timestamp":1729609012000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":1,"title":["Dual PPAR-\u03b1\/\u03b3 enhances beta cell identity, preserving islet structure in HF-fed mice"],"prefix":"10.1530","volume":"264","author":[{"given":"Aline","family":"Fernandes-da-Silva","sequence":"first","affiliation":[{"name":"Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Centre, Institute of Biology, Rio de Janeiro State University 1 , ,","place":["Rio de Janeiro, 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