title: Reduction of renal lipid content and proteinuria by a PPAR-γ agonist in a rat model of angiotensin II-induced hypertension.
abstract: An excess of lipids may accumulate in the kidney in conditions such as diabetes and hypertension, and can potentially cause renal injury. We previously reported that an infusion of angiotensin II into a rat induced deposition of lipids in the renal tubular epithelial cells. Here we have examined the effect of pioglitazone, an agonist of the peroxisome proliferator-activated receptor-γ (PPAR-γ), on renal lipid accumulation and renal injury induced by angiotensin II infusion. Pioglitazone treatment (2.5mg/kg/day) reduced the amount of triglycerides in the kidney of the angiotensin II-induced hypertensive rat without significantly altering either blood pressure levels or mRNA expression of lipogenic genes in the kidney. In addition, pioglitazone, either alone or in conjunction with angiotensin II, increased the expression of phosphorylated, but not total, AMP-activated protein kinase (AMPK). Proteinuria and kidney weight in the angiotensin II-infused rat were significantly decreased by pioglitazone treatment. In addition, pioglitazone suppressed iron deposition and ferritin protein induction, but did not alter upregulated expression of the antioxidative molecule, heme oxygenase-1, in the kidney of the angiotensin II-infused rat. These findings suggested that pioglitazone suppressed the angiotensin II-induced increase in renal lipid content by inhibiting its proteinuric action, but not by direct alteration of the expression or activity of lipid metabolism-related genes. Reduction of lipotoxic renal damage may represent one of the renoprotective effects provided by pioglitazone in hypertension with activation of the renin-angiotensin system.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Makiko
authors.initials: M
authors.lastname: Hongo
authors.forename: Kan
authors.initials: K
authors.lastname: Saito
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Ishizaka
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005293:Ferritins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008297:Male; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D011507:Proteinuria / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D000804:Angiotensin II; D005293:Ferritins; D007501:Iron; D051547:Heme Oxygenase-1; D000077205:Pioglitazone