Biology and toxicology of PPARg ligands

Tugwood, Jonathan; Montague, Carl

doi:10.1191/0960327102ht282oa

Cited by 22 publications

(19 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2). These observations are in agreement with the unaltered FA uptake capacity in skeletal muscle and heart from Rgz-treated obese rats (this study) and with the low expression of PPAR ␥ in these tissues (33).…”

Section: Changes In Membrane Fatty Acid Transport Protein Levels Aftesupporting

confidence: 80%

Divergent effects of rosiglitazone on protein-mediated fatty acid uptake in adipose and in muscle tissues of Zucker rats

Coort

Coumans

Bonen

et al. 2005

Journal of Lipid Research

View full text Add to dashboard Cite

Thiazolidinediones (TZDs) increase tissue insulin sensitivity in diabetes. Here, we hypothesize that, in adipose tissue, skeletal muscle, and heart, alterations in proteinmediated FA uptake are involved in the effect of TZDs. As a model, we used obese Zucker rats, orally treated for 16 days with 5 mg rosiglitazone (Rgz)/kg body mass/day. In adipose tissue from Rgz-treated rats, FA uptake capacity increased by 2.0-fold, coinciding with increased total contents of fatty acid translocase (FAT/CD36; 2.3-fold) and fatty acid transport protein 1 (1.7-fold) but not of plasmalemmal fatty acid binding protein, whereas only the plasmalemmal content of FAT/CD36 was changed (increase of 1.7-fold). The increase in FA uptake capacity of adipose tissue was associated with a decline in plasma FA and triacylglycerols (TAGs), suggesting that Rgz treatment enhanced plasma FA extraction by adipocytes. In obese hearts, Rgz treatment had no effect on the FA transport system, yet the total TAG content decreased, suggesting enhanced insulin sensitivity. Also, in skeletal muscle, the FA transport system was not changed. However, the TAG content remained unaltered in skeletal muscle, which coincided with increased cytoplasmic adipose-type FABP content, suggesting that increased extramyocellular TAGs mask the decline of intracellular TAG in muscle. In conclusion, our study implicates FAT/CD36 in the mechanism by which Rgz increases tissue insulin sensitivity.-Coort, S. L. M., W.

show abstract

Section: Changes In Membrane Fatty Acid Transport Protein Levels Aftesupporting

confidence: 80%

Divergent effects of rosiglitazone on protein-mediated fatty acid uptake in adipose and in muscle tissues of Zucker rats

Coort

Coumans

Bonen

et al. 2005

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Similarly, edema and water retention are frequently occurring side effects in many patients treated with TZDs [3, 34, 35, 66, 67]. This effect can normally be treated with diuretics; however, this cannot fully restore the interstitial fluid volume in TZD-treated diabetic or atherosclerotic patients if glomerulosclerosis or diabetic glomerulonephritis with osmotic diuresis has developed.…”

Section: Volume Overload Is the Adverse Effect Of Pparγ Activationmentioning

confidence: 99%

PPARs in the Renal Regulation of Systemic Blood Pressure

Röszer

Ricote

2010

PPAR Research

View full text Add to dashboard Cite

Recent research has revealed roles for the peroxisome proliferator activated receptor (PPAR) family of transcription factors in blood pressure regulation, expanding the possible therapeutic use of PPAR ligands. PPARα and PPARγ modulate the renin-angiotensin-aldosterone system (RAAS), a major regulator of systemic blood pressure and interstitial fluid volume by transcriptional control of renin, angiotensinogen, angiotensin converting enzyme (ACE) and angiotensin II receptor 1 (AT-R1). Blockade of RAAS is an important therapeutic target in hypertension management and attenuates microvascular damage, glomerular inflammation and left ventricular hypertrophy in hypertensive patients and also show antidiabetic effects. The mechanisms underlying the benefits of RAAS inhibition appear to involve PPARγ-regulated pathways. This review summarizes current knowledge on the role of PPARs in the transcriptional control of the RAAS and the possible use of PPAR ligands in the treatment of RAAS dependent hypertension.

show abstract

“…In contrast to classical prostaglandins, which bind to cell surface G protein-coupled receptors, 15d-PG J2 is a natural ligand of a nuclear receptor, the peroxisome proliferator-activated receptor (PPAR) ␥. This receptor behaves as a ligand-activated transcription factor through its DNA binding domain, which recognizes response elements in the promoter of some target genes linked to apoptosis, cell proliferation, and differentiation and inflammation (13,14). Recent data show the presence of PPAR␥ in rat cartilage and human synovial tissues (15) and indicate that 15d-PG J2 is the most potent endogenous ligand for PPAR␥ yet discovered (16).…”

mentioning

confidence: 99%