title: Tesaglitazar, a dual peroxisome proliferator-activated receptor agonist (PPAR alpha/gamma), improves metabolic abnormalities and reduces renal injury in obese Zucker rats.
abstract: Metabolic syndrome increases the risk of developing diabetes as well as cardiovascular and kidney diseases. This research studied the effects of tesaglitazar, a dual-acting peroxisome proliferator-activated receptor (PPAR)alpha/gamma agonist, on metabolic abnormalities and kidney injury in obese Zucker rats (OZR). Lean Zucker rats (LZR) and OZR were used as control groups. Tesaglitazar (1 micromol/kg/day) was given for 8 weeks in the treatment group (OZR-T). Metabolic parameters, 24-hour urine albumin excretion, and tail blood pressure were measured. Glomerular filtration rate by inulin clearance, abdominal fat and renal histology were determined at the end of the study. In comparison with the OZR and OZR-T groups, the LZR control animals' parameters were significantly more favorable in all measures. Tesaglitazar treatment in OZR significantly reduced nonfasting glucose, C-reactive protein levels and improved dyslipidemia. Body weight, blood pressure and urine albumin excretion were lower, but the adjusted glomerular filtration rate higher, in the OZR-T group than in the OZR controls. Glomerular area, mesangial expansion and tubulointerstitial changes were ameliorated, and the glomerular expression of desmin was markedly more decreased in the OZR-T group than in the OZR controls. Therefore, the PPAR alpha/gamma agonist tesaglitazar significantly improved metabolic abnormalities and renal function, decreased blood pressure, and protected against glomerular and interstitial damage in OZR.
authors.affiliation: Section of Nephrology and Hypertension, LSU Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liao
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Soltani
authors.forename: Philip
authors.initials: P
authors.lastname: Ebenezer
authors.forename: Angel A
authors.initials: AA
authors.lastname: Isidro-Carrión
authors.forename: Rubin
authors.initials: R
authors.lastname: Zhang
authors.forename: Arshad
authors.initials: A
authors.lastname: Asghar
authors.forename: Erwin
authors.initials: E
authors.lastname: Aguilar
authors.forename: Joseph
authors.initials: J
authors.lastname: Francis
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Hu
authors.forename: León
authors.initials: L
authors.lastname: Ferder
authors.forename: Efrain
authors.initials: E
authors.lastname: Reisin
mesh_terms: D000476:Alkanesulfonates / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007674:Kidney Diseases / Q000517:prevention & control*; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology*; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010666:Phenylpropionates / Q000627:therapeutic use*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D000476:Alkanesulfonates; D047493:PPAR alpha; D047495:PPAR gamma; D010666:Phenylpropionates; C501413:tesaglitazar