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Peroxisome proliferator-activated receptor-gamma expression in the lung tissue of obese rats.

ABSTRACT: PURPOSE: Obesity is a risk factor for asthma and type II diabetes. Peroxisome proliferator- activated receptor (PPAR)-? has been suggested to regulate inflammatory responses in diabetes and asthma. We investigated whether PPAR-?, PPAR-?, adiponectin receptors (AdipoR1, AdipoR2), leptin, and tumor necrosis factor (TNF)-? are expressed in rat lung tissues and whether the expression differs between obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long Evans Tokushima Otsuka (LETO) rats. MATERIALS AND METHODS: Obese and lean rats were given with a high fat diet or a 30% restricted diet for 32 weeks, and their blood glucose levels and weights were monitored. After 32 weeks, mRNA levels of PPAR-?, PPAR-?, AdipoR1, AdipoR2, leptin, and TNF-? in lung tissues were measured using real time PCR. RESULTS: PPAR-?, PPAR-?, AdipoR1, AdipoR2, leptin, and TNF-? were expressed in both obese and lean rat lung tissues. Increased serum glucose levels on intraperitoneal glucose tolerance testing and a higher weight gain at 32 weeks were observed in OLETF control rats compared to OLETF diet restricted rats. PPAR-? expression was markedly elevated in obese control and diet restricted rats compared to lean rats, although PPAR-? expression in obese rats was not affected by diet restriction. Leptin was highly expressed in OLETF rats compared to LETO rats. TNF-? expression was enhanced in OLETF control rats compared LETO diet restricted rats, and decreased by diet restriction. PPAR-?, AdipoR1, and AdipoR2 expression were not significantly different between obese and lean rats. CONCLUSION: PPAR-? was highly expressed in the lung tissues of obese rats and may be a novel treatment target for regulating lung inflammation associated with obesity.

SUBMITTER: Hwang SJ

PROVIDER: S-EPMC3101042 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Peroxisome proliferator-activated receptor-gamma expression in the lung tissue of obese rats.

Hwang Su Jin SJ Kim Jung Ho JH Shim Jae Won JW Kim Deok Soo DS Jung Hye Lim HL Park Moon Soo MS Lee Won Young WY Kim Se-Yeon SY Shim Jung Yeon JY

Yonsei medical journal 20110501 3

<h4>Purpose</h4>Obesity is a risk factor for asthma and type II diabetes. Peroxisome proliferator- activated receptor (PPAR)-γ has been suggested to regulate inflammatory responses in diabetes and asthma. We investigated whether PPAR-α, PPAR-γ, adiponectin receptors (AdipoR1, AdipoR2), leptin, and tumor necrosis factor (TNF)-α are expressed in rat lung tissues and whether the expression differs between obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long Evans Tokushima Otsuka (LETO) ra ...[more]

PMID: 21488194

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Project description:ObjectiveNuclear receptor Peroxisome Proliferator-Activated Receptor γ (PPARγ) is a promising target for the treatment of type 2 diabetes. The antidiabetic drug thiazolidinediones (TZDs) are potent insulin sensitizers as full agonists of PPARγ, but cause unwanted side effects. Recent discoveries have shown that TZDs improve insulin sensitivity by blocking PPARγ phosphorylation at S273, which decouples the full agonism-associated side effects. PPARγ ligands that act through the blockage of PPARγ phosphorylation but lack the full agonist activity would be expected to improve insulin sensitivity without TZD-associated side effects, however, chemicals that carry such traits and bind to PPARγ with high-affinity are lacking. Moreover, TZDs are known to promote white-to-brown adipocyte conversion and energy expenditure and appear to require their full agonism on PPARγ for this activity. It is unknown whether a partial or non-TZD agonist of PPARγ is capable of promoting browning effect. In this study, we developed a novel non-TZD partial agonist of PPARγ and investigated its function on insulin sensitivity and white-to-brown conversion and energy expenditure in diet-induced obese mice.MethodsA novel indole-based chemical WO95E was designed via medicinal chemistry and tested for PPARγ binding and activity and for the effect on PPARγ phosphorylation. Diet-induced obese mice were administered with WO95E for 4 weeks. Insulin sensitivity, glucose tolerance, body weight, fat tissue weight, adipocyte size, morphology, energy expenditure, and expression levels of genes involved in PPARγ activity, thermogenesis/browning, and TZD-related side effects were evaluated.ResultsWO95E binds to PPARγ with high affinity and acts as a PPARγ partial agonist. WO95E inhibits PPARγ phosphorylation and regulates PPARγ phosphorylation-dependent genes. WO95E ameliorates insulin resistance and glucose tolerance in mice of diet-induced obesity, with minimal TZD use-associated side effects. We found that WO95E promotes white-to-brown adipocyte conversion and energy expenditure and hence protects against diet-induced obesity. WO95E decreases the size of adipocytes and suppresses adipose tissue inflammation. WO95E also suppresses obesity-associated liver steatosis.ConclusionsWO95E improves insulin sensitivity and glucose homeostasis and promotes browning and energy expenditure by acting as a novel PPARγ phosphorylation inhibitor/partial agonist. Our findings suggest the potential of this compound or its derivative for the therapeutic treatment of insulin resistance and obesity.

Dataset Information

Peroxisome proliferator-activated receptor-gamma expression in the lung tissue of obese rats.

Publications

Peroxisome proliferator-activated receptor-gamma expression in the lung tissue of obese rats.

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