Peroxisome proliferator-activated receptor effects

The thiazolidinediones have also been reported to act as inhibitors of the respiratory chain at high concentrations, and this appears to account for their ability to activate AMGPK in cultured cells. However, the primary target of the thiazolidinediones appears to be the peroxisome proliferator-activated receptor-y ( PPAR-y), a member of the nuclear receptor superfamily expressed in adipocytes. One of the major effects of stimulation of PPAR-y in adipocytes is the release ofthe... 

Thiazolidinediones (PPARy-agonists) Thiazolidine-diones ( pioglitazone, rosiglitazone) lower blood glucose levels in animal models of insulin resistance and also in insulin resistant patients. They are agonists of the peroxisome proliferator-activated receptor y (PPARy). Because they enhance the effect of insulin and reduce serum insulin levels in insulin resistant patients, thiazolidinediones are usually referred to as insulin sensitizers . 

Peroxisome Proliferator-Activated Receptors. Table 1 PPARa target tissues, cellular effects, and physiological effects... 

Palakurthi, S. S., Aktas, H., Grubissich, L. M., Mortensen, R. M., and Halperin, J. A. (2001). Anticancer effects of thiazolidinediones are independent of peroxisome proliferator-activated receptor gamma and mediated by inhibition of translation initiation. Cancer Res. 61, 6213-6218. 

Ruyter B., O. Andersen, A. Dehli, A.-K. Ostlrmd Farrants, T. Gjoen, and M.S. Thomassen (1997). Peroxisome proliferator activated receptors in Atlantic salmon Salmo solar)-. Effects on PPAR transcription and acyl-CoA oxidase activity in hepatocytes by peroxisome proliferators and fatty acids. BBA-Lipids and Lipid Metabolism 1348 331-338. 

Tugwood, J.D., Holden, P.R., James, N.H., Prince, R.A. Roberts, R.A. (1998) A peroxisome proliferator-activated receptor-alpha (PPARa) cDNA cloned from guinea-pig liver encodes a protein with similar properties to the mouse PPARa implications for species differences in responses to peroxisome proliferators. Arch. Toxicol., 72, 169-177 Turner, J.H., Petricciani, J.C., Crouch, M.L. Wenger, S. (1974) An evaluation of the effects of diethylhexyl phthalate (DEHP) on mitotically capable cells in blood packs. Transfusion, 14, 560-566... 

The effect of dietary fats on hypertriglyceridemia is dependent on the disposition of double bonds in the fatty acids. Omega-3 fatty acids found in fish oils, but not those from plant sources, activate peroxisome proliferator-activated receptor-alpha (PPAR- ) and can induce profound reduction of triglycerides in some patients. They also have antiinflammatory and antiarrhythmic activities. In contrast, the omega-6 fatty acids present in vegetable oils may cause triglycerides to increase. 

Hepatic and peripheral effects of fibrates. These effects are mediated by activation of peroxisome proliferator-activated receptor-a, which modulates the expression of several proteins. LPL, lipoprotein lipase VLDL, very-low-density lipoproteins. 

Covers the effects of diet on the regulation of gene expression, considering the role of peroxisome proliferator-activated receptors (PPARs)... 

Some effects of prostaglandins are mediated through cell surface G-protein coupled receptors (see Chapter ll).306 Some other prostanoids bind to and activate nuclear peroxisome proliferator-activated receptors.306 PGJ2 may inhibit fatty acid synthesis and fat deposition in adipose tissue through these receptors. Some of the prostanoid derivatives enter membranes and may become incorporated into phospholipids and exert their effects there. 

Philips J-C, Petite C, Willi J-P, Buchegger F, Meier CA. Effect of peroxisome proliferator-activated receptor 8 agonist rosiglitazone on dedifferentiated thyroid cancers. Nucl Med Comm 2004 25 1183-6. 

The exact mechanism of these drugs is unclear, but they probably work by binding to a specific nuclear receptor known as the peroxisome proliferator activated receptor.52,141 This receptor, found primarily in the liver and adipose tissues, affects the transcription of genes that affect lipid metabolism.89 Fibrates activate this receptor, thereby mediating several changes at the nuclear level that ultimately cause a decrease in triglycerides and other beneficial changes in plasma lipid metabolism.30,52 In a manner similar to the statins, fibrates may also exert anti-inflammatory, antioxidant, and other beneficial effects in addition to their positive effects on plasma lipids.42,49... 

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