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==Function== | ==Function== | ||
[[Image: PPAR_Mechanism.png|400px| | [[Image: PPAR_Mechanism.png|400px|left|thumb|Figure 2: Mechanism of Human PPARα & PPARγ]] | ||
The common functionality between the three isoforms consists of binding with a heterodimeric protein, Retinoid X Receptor (RXR) <ref name="PPAR8">PMID:11457759</ref><ref name="PPAR9">PMID:10947870</ref>, to regulate gene expression by recognizing specific DNA elements known as Peroxisome Proliferator Response Elements (PPREs). The heterodimeric transcription factor complex then binds to cognate sequences in promoter regions of target genes involved in the catabolism of fatty acids <ref name="PPAR9"/>. Transcriptional activation or repression of the target gene is more complex than simple binding of the PPAR/RXR heterodimer, there is an initial association with transcriptional corepressors and recruitment of activators that occurs in association to ligand activation <ref name="PPAR2"/><ref name="PPAR7"/><ref name="PPAR9"/>. | The common functionality between the three isoforms consists of binding with a heterodimeric protein, Retinoid X Receptor (RXR) <ref name="PPAR8">PMID:11457759</ref><ref name="PPAR9">PMID:10947870</ref>, to regulate gene expression by recognizing specific DNA elements known as Peroxisome Proliferator Response Elements (PPREs). The heterodimeric transcription factor complex then binds to cognate sequences in promoter regions of target genes involved in the catabolism of fatty acids <ref name="PPAR9"/>. Transcriptional activation or repression of the target gene is more complex than simple binding of the PPAR/RXR heterodimer, there is an initial association with transcriptional corepressors and recruitment of activators that occurs in association to ligand activation <ref name="PPAR2"/><ref name="PPAR7"/><ref name="PPAR9"/>. | ||
PPAR-alpha is involved in regulating the expression of genes involved in the peroxisomal and mitochondrial Beta oxidation pathways such as Acyl-CoA oxidase, Enol-Co dehydrogenase/hydratase, Malic enzyme and various others <ref name="PPAR9"/>. Activated PPAR-alpha contributes to increased breakdown of triglycerides and fatty acids, increased uptake of cellular fatty acids, and reduction in triglyceride and fatty acid synthesis. PPAR alpha displays the greatest amount of activity in the post-absorptive state or fasting state within animals. In the liver, fatty acids are oxidized to acetyl-CoA and/or ketone bodies, in which both processes are strongly stimulated by the expression of PPAR alpha <ref name="PPAR8"/>. Since fatty acids act as ligands of PPAR alpha, it is possible that fatty acids liberated from adipose tissue can stimulate their own metabolism by activating PPAR alpha receptors. | PPAR-alpha is involved in regulating the expression of genes involved in the peroxisomal and mitochondrial Beta oxidation pathways such as Acyl-CoA oxidase, Enol-Co dehydrogenase/hydratase, Malic enzyme and various others <ref name="PPAR9"/>. Activated PPAR-alpha contributes to increased breakdown of triglycerides and fatty acids, increased uptake of cellular fatty acids, and reduction in triglyceride and fatty acid synthesis. PPAR alpha displays the greatest amount of activity in the post-absorptive state or fasting state within animals. In the liver, fatty acids are oxidized to acetyl-CoA and/or ketone bodies, in which both processes are strongly stimulated by the expression of PPAR alpha <ref name="PPAR8"/>. Since fatty acids act as ligands of PPAR alpha, it is possible that fatty acids liberated from adipose tissue can stimulate their own metabolism by activating PPAR alpha receptors. | ||
[[Image: PPARa_Mech.gif|300px|right|thumb|Figure 3: Ligands and target genes of Human PPARα]] | |||
All three isoforms of PPAR are becoming more and more of an interest in scientific communities as possible mechanisms of treatment in various diseases and conditions such as Diabetes Mellitus and obesity. Fibrates, which include fenofibrate, bind with PPAR alpha in high affinity and act to lower plasma triglyceride levels and increase high density lipoprotein levels<ref name="PPAR10">PMID:10839530</ref>. Therefore, fibrates may also have an anti-diabetic effect as a consequence of their hypolipidaemic action. PPAR alpha may also have a hand in the prevention of atherosclerosis by decreasing the plasma concentrations of pro-atherosclerosis proteins such as fibrinogen and C-reactive protein <ref name="PPAR10"/>. Much of the current research involved with PPARs is directed towards the identification of highly specific agonists and antagonists for treatment of numerous metabolic diseases and conditions. | All three isoforms of PPAR are becoming more and more of an interest in scientific communities as possible mechanisms of treatment in various diseases and conditions such as Diabetes Mellitus and obesity. Fibrates, which include fenofibrate, bind with PPAR alpha in high affinity and act to lower plasma triglyceride levels and increase high density lipoprotein levels<ref name="PPAR10">PMID:10839530</ref>. Therefore, fibrates may also have an anti-diabetic effect as a consequence of their hypolipidaemic action. PPAR alpha may also have a hand in the prevention of atherosclerosis by decreasing the plasma concentrations of pro-atherosclerosis proteins such as fibrinogen and C-reactive protein <ref name="PPAR10"/>. Much of the current research involved with PPARs is directed towards the identification of highly specific agonists and antagonists for treatment of numerous metabolic diseases and conditions. | ||
