PPARγ Agonists, Modulation of Ion Transporters, and Fluid Retention

Nofziger, Charity; Blazer‐Yost, Bonnie L.

doi:10.1681/asn.2009060673

Cited by 16 publications

(10 citation statements)

References 15 publications

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“…Age-related mechanisms such as stress-induced cellular senescence associate with AKI, 90 and use of peroxisome proliferator-activated preceptor ␥ agonists are protective in experimental models 91 but in humans have adverse effects (fluid retention among others) that could be problematic for the elderly. 92 Overall expression of the senescence marker p16(INK4A) and the percentage of cells expressing p16(INK4A), particularly in the glomerulus, tubules, and interstitial space, are higher in older kidneys than in younger ones. 93,94 Telomere shortening, 42 Dicer-associated microRNAs, 95 and heme oxygenase-regulated autophagy 96 are important new modulators for risk for AKI.…”

Section: Mechanisms Underlying Akimentioning

confidence: 98%

Acute Kidney Injury in Older Adults

Anderson¹,

Eldadah²,

Halter³

et al. 2011

Journal of the American Society of Nephrology

189

136

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Section: Mechanisms Underlying Akimentioning

confidence: 98%

Acute Kidney Injury in Older Adults

Anderson¹,

Eldadah²,

Halter³

et al. 2011

Journal of the American Society of Nephrology

189

136

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“…PPAR- γ is widely expressed in several organs including kidneys and known to be activated by fatty acids [6, 7]. Antidiabetic agents, pioglitazone (PIO), troglitazone, ciglitazone, and rosiglitazone, are used to control blood sugar levels in patients with diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

Global Gene Expression Profiling in PPAR-γAgonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

et al. 2012

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Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-γ agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism.

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“…For example, synthetic PPAR γ agonists, thiazolidinediones, have been widely used as insulin sensitizing agents for treatment of type 2 diabetes; synthetic PPAR α agonists such as clofibrate and fenofibrate have been used in clinics for more than 30 years as lipid lowering agents [5–8]. Unfortunately, these synthetic agents are often associated with various toxicities [7, 9–11]. The goal of the present study was to examine the therapeutic potential of OA-NO 2 in an experimental model of obesity and metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

Effects of Endogenous PPAR Agonist Nitro-Oleic Acid on Metabolic Syndrome in Obese Zucker Rats

et al. 2010

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Nitroalkene derivatives of nitro-oleic acid (OA-NO2) are endogenous lipid products with novel signaling properties, particularly the activation of PPARs. The goal of this proposal was to examine the therapeutic potential of this OA-NO2 in treatment of obesity and obesity-related conditions in obese Zucker rats. The animals were randomly divided to receive OA-NO2, oleic acid (OA), both at 7.5 μg/kg/d, or vehicle ethanol via osmotic mini-pumps for 2 weeks. Following OA-NO2 treatment, food intake was decreased as early as the first day and this effect appeared to persist throughout the experimental period. At day 14, body weight gain was significantly reduced by OA-NO2 treatment. This treatment significantly reduced plasma triglyceride and almost normalized plasma free fatty acid and significantly increased plasma high-density lipid (HDL). The plasma TBARS and proteinuria were paralelly decreased. In contrast, none of these parameters were affected by OA treatment. After 14 days of OA-NO2 treatment, hematocrit, a surrogate of fluid retention associated with PPARγ agonists, remained unchanged. Together, these data demonstrated that OA-NO2 may offer an effective and safe therapeutic intervention for obesity and obesity-related conditions.

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PPARγ Agonists, Modulation of Ion Transporters, and Fluid Retention

Cited by 16 publications

References 15 publications

Acute Kidney Injury in Older Adults

Acute Kidney Injury in Older Adults

Global Gene Expression Profiling in PPAR-γAgonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

Effects of Endogenous PPAR Agonist Nitro-Oleic Acid on Metabolic Syndrome in Obese Zucker Rats

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