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==Ligand Interactions==

[[Image: 1I7G.jpg|400px|right|thumb|Figure 1: Ligand binding domain of PPARα in complex with agonist Az242. [[1i7g]] ]]

PPAR alpha ligands can consist of either synthetic drugs (exogenous) or biological molecules (endogenous). '''Most common biological molecules that serve as ligands for human PPAR alpha are fatty acids and fatty acid derivatives''' <ref name="PPAR1"/><ref name="PPAR2"/>. Several enzymes such as 8-, 12-, 15-, and 5-[http://en.wikipedia.org/wiki/Lipoxygenase lipoxygenases], the [http://en.wikipedia.org/wiki/Cyclooxygenase cyclooxygenases] and [http://en.wikipedia.org/wiki/Cytochrome_P450 cytochrome P450] utilize fatty acids as substrates to produce putative PPAR alpha ligands. [http://en.wikipedia.org/wiki/Leukotriene_B4 Leukotriene B4} is a well-known putative PPAR alpha ligand, as well as 19- and 20- hydroxyeicosatetraeonic acid, generated from cytochrome P450 as a conversion of arachidonic acid. Oleylethanolamide, a naturally occurring lipid, has also been identified as a high affinity PPAR alpha ligand regulating PPAR alpha activity and lipid metabolism <ref name="PPAR6">PMID:20414453</ref>.

PPAR alpha ligands can consist of either synthetic drugs (exogenous) or biological molecules (endogenous). '''Most common biological molecules that serve as ligands for human PPAR alpha are fatty acids and fatty acid derivatives''' <ref name="PPAR1"/><ref name="PPAR2"/>. Several enzymes such as 8-, 12-, 15-, and 5-[http://en.wikipedia.org/wiki/Lipoxygenase lipoxygenases], the [http://en.wikipedia.org/wiki/Cyclooxygenase cyclooxygenases] and [http://en.wikipedia.org/wiki/Cytochrome_P450 cytochrome P450] utilize fatty acids as substrates to produce putative PPAR alpha ligands. [http://en.wikipedia.org/wiki/Leukotriene_B4 Leukotriene B4] is a well-known putative PPAR alpha ligand, as well as 19- and 20- hydroxyeicosatetraeonic acid, generated from cytochrome P450 as a conversion of arachidonic acid. Oleylethanolamide, a naturally occurring lipid, has also been identified as a high affinity PPAR alpha ligand regulating PPAR alpha activity and lipid metabolism <ref name="PPAR6">PMID:20414453</ref>.

Proliferation of peroxisomes in liver parenchymal cells and upregulated transcriptional activity of fatty acid oxidation system genes are the general hallmarks of exogenous ligand-induced responses, as observed in rat and mouse liver. These include, but not limited to, hypolipidemic drugs such as clofibrate, fenofibrate, bezafibrate, and ciprofibrate <ref name="PPAR6"/>.

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[[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 metabolic disorders 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 metabolic disorders 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 [http://en.wikipedia.org/wiki/Fibrinogen fibrinogen] and [http://en.wikipedia.org/wiki/C-reactive_protein 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.

=Additional Resources=

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@@ Line 16: / Line 16: @@
 ==Ligand Interactions==
 [[Image: 1I7G.jpg|400px|right|thumb|Figure 1: Ligand binding domain of PPARα in complex with agonist Az242. [[1i7g]] ]]
-PPAR alpha ligands can consist of either synthetic drugs (exogenous) or biological molecules (endogenous). '''Most common biological molecules that serve as ligands for human PPAR alpha are fatty acids and fatty acid derivatives''' <ref name="PPAR1"/><ref name="PPAR2"/>. Several enzymes such as 8-, 12-, 15-, and 5-[http://en.wikipedia.org/wiki/Lipoxygenase lipoxygenases], the [http://en.wikipedia.org/wiki/Cyclooxygenase cyclooxygenases] and [http://en.wikipedia.org/wiki/Cytochrome_P450 cytochrome P450] utilize fatty acids as substrates to produce putative PPAR alpha ligands. [http://en.wikipedia.org/wiki/Leukotriene_B4 Leukotriene B4} is a well-known putative PPAR alpha ligand, as well as 19- and 20- hydroxyeicosatetraeonic acid, generated from cytochrome P450 as a conversion of arachidonic acid. Oleylethanolamide, a naturally occurring lipid, has also been identified as a high affinity PPAR alpha ligand regulating PPAR alpha activity and lipid metabolism <ref name="PPAR6">PMID:20414453</ref>.
+PPAR alpha ligands can consist of either synthetic drugs (exogenous) or biological molecules (endogenous). '''Most common biological molecules that serve as ligands for human PPAR alpha are fatty acids and fatty acid derivatives''' <ref name="PPAR1"/><ref name="PPAR2"/>. Several enzymes such as 8-, 12-, 15-, and 5-[http://en.wikipedia.org/wiki/Lipoxygenase lipoxygenases], the [http://en.wikipedia.org/wiki/Cyclooxygenase cyclooxygenases] and [http://en.wikipedia.org/wiki/Cytochrome_P450 cytochrome P450] utilize fatty acids as substrates to produce putative PPAR alpha ligands. [http://en.wikipedia.org/wiki/Leukotriene_B4 Leukotriene B4] is a well-known putative PPAR alpha ligand, as well as 19- and 20- hydroxyeicosatetraeonic acid, generated from cytochrome P450 as a conversion of arachidonic acid. Oleylethanolamide, a naturally occurring lipid, has also been identified as a high affinity PPAR alpha ligand regulating PPAR alpha activity and lipid metabolism <ref name="PPAR6">PMID:20414453</ref>.
 Proliferation of peroxisomes in liver parenchymal cells and upregulated transcriptional activity of fatty acid oxidation system genes are the general hallmarks of exogenous ligand-induced responses, as observed in rat and mouse liver. These include, but not limited to, hypolipidemic drugs such as clofibrate, fenofibrate, bezafibrate, and ciprofibrate <ref name="PPAR6"/>.
@@ Line 30: / Line 30: @@
 [[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 metabolic disorders 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 metabolic disorders 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 [http://en.wikipedia.org/wiki/Fibrinogen fibrinogen] and [http://en.wikipedia.org/wiki/C-reactive_protein 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.
 =Additional Resources=