{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T21:36:07Z","timestamp":1787520967314,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T00:00:00Z","timestamp":1489449600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2017,3]]},"abstract":"Abstract<\/jats:title>The leptin\u2010deficient BTBR<\/jats:styled-content>ob\/ob mouse develops progressive albuminuria and morphological lesions similar to human diabetic nephropathy (DN<\/jats:styled-content>), although whether glomerular hyperfiltration, a recognized feature of early DN<\/jats:styled-content> that may contribute to renal injury, also occurs in this model is not known. Leptin replacement has been shown to reverse the signs of renal injury in this model, but in contrast, the expected renoprotection by angiotensin\u2010converting enzyme (ACE<\/jats:styled-content>) inhibition in BTBR<\/jats:styled-content>ob\/ob mice seems to be limited. Therefore, to investigate the potential renal benefits of improved metabolic control in this model, we studied the effect of treatment with the dual peroxisome proliferator\u2010activated receptor (PPAR<\/jats:styled-content>) \u03b1<\/jats:italic>\/\u03b3<\/jats:italic> agonist AZD<\/jats:styled-content>6610 and compared it with the ACE<\/jats:styled-content> inhibitor enalapril. AZD<\/jats:styled-content>6610 lowered plasma glucose and triglyceride concentrations and increased liver size, but had no significant effect in reducing albuminuria, whereas enalapril did have an effect. Nephrin and WT<\/jats:styled-content>1 mRNA<\/jats:styled-content> expression decreased in the kidneys of BTBR<\/jats:styled-content>ob\/ob mice, consistent with podocyte injury and loss, but was unaffected by either drug treatment: at the protein level, both nephrin and WT<\/jats:styled-content>1\u2010positive cells per glomerulus were decreased. Mesangial matrix expansion was reduced in AZD<\/jats:styled-content>6610\u2010treated mice. GFR<\/jats:styled-content>, measured by creatinine clearance, was increased in BTBR<\/jats:styled-content>ob\/ob mice, but unaffected by either treatment. Unexpectedly, enalapril\u2010treated mice showed intrarenal arteriolar vascular remodeling with concentric thickening of vessel walls. In summary, we found that the BTBR<\/jats:styled-content>ob\/ob mouse model shows some similarities to the early changes seen in human DN<\/jats:styled-content>, but that ACE<\/jats:styled-content> inhibition or PPAR<\/jats:styled-content>\u03b1<\/jats:italic>\/\u03b3<\/jats:italic> agonism afforded limited or no kidney protection.<\/jats:p>","DOI":"10.14814\/phy2.13186","type":"journal-article","created":{"date-parts":[[2017,3,15]],"date-time":"2017-03-15T00:10:18Z","timestamp":1489536618000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The effects of dual PPAR\u03b1<\/i>\/\u03b3<\/i> agonism compared with ACE inhibition in the BTBRob\/ob mouse model of diabetes and diabetic nephropathy"],"prefix":"10.14814","volume":"5","author":[{"given":"Anette","family":"Ericsson","sequence":"first","affiliation":[{"name":"Cardiovascular & Metabolic Disease Innovative Medicines AstraZeneca R&D Gothenburg M\u00f6lndal 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