{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:34:30Z","timestamp":1771472070695,"version":"3.50.1"},"reference-count":114,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Prolyl hydroxylase (PH) enzymes control the degradation of hypoxia-inducible factor (HIF), a transcription factor known to regulate erythropoiesis, angiogenesis, glucose metabolism, cell proliferation, and apoptosis. HIF-PH inhibitors (HIF-PHIs) correct anemia in patients with renal disease and in animal models of anemia and kidney disease. However, the effects of HIF-PHIs on comorbidities associated with kidney disease remain largely unknown. We evaluated the effects of the HIF-PHI FG-2216 in obese ZSF1 (Ob-ZSF1) rats, an established model of kidney failure with metabolic syndrome. Following unilateral nephrectomy (Nx) at 8 weeks of age, rats were treated with 40 mg\/kg FG-2216 or vehicle by oral gavage three times per week for up to 18 weeks. FG-2216 corrected blood hemoglobin levels and improved kidney function and histopathology in Nx-Ob-ZSF1 rats by increasing the glomerular filtration rate, decreasing proteinuria, and reducing peritubular fibrosis, tubular damage, glomerulosclerosis and mesangial expansion. FG-2216 increased renal glucose excretion and decreased body weight, fat pad weight, and serum cholesterol in Nx-Ob-ZSF1 rats. Additionally, FG-2216 corrected hypertension, improved diastolic and systolic heart function, and reduced cardiac hypertrophy and fibrosis. In conclusion, the HIF-PHI FG-2216 improved renal and cardiovascular outcomes, and reduced obesity in a rat model of kidney disease with metabolic syndrome. Thus, in addition to correcting anemia, HIF-PHIs may provide renal and cardiac protection to patients suffering from kidney disease with metabolic syndrome.<\/jats:p>","DOI":"10.1371\/journal.pone.0255022","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T17:34:43Z","timestamp":1627925683000},"page":"e0255022","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["A small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase improves obesity, nephropathy and cardiomyopathy in obese ZSF1 rats"],"prefix":"10.1371","volume":"16","author":[{"given":"Pierre 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