General Information:

Id: 824 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Obesity - [OMIM]
Mammalia
review
Reference: Sugden MC et al.(2010) PPAR control: its SIRTainly as easy as PGC J. Endocrinol. 2: 93-104 [PMID: 19770177]

Interaction Information:

Comment Ligand binding to PPAR-alpha causes PPAR-alpha to heterodimerize with the RXR and recruit coactivators to activate a program of lipid-induced activation of genes encoding proteins involved in fatty acid uptake, activation, and oxidation.
Formal Description
Interaction-ID: 4766

gene/protein

PPARA

interacts (colocalizes) with

gene/protein

RXR

upon ligand binding
Drugbank entries Show/Hide entries for PPARA
Comment PPAR-alpha target genes include carnitine palmitoyltransferase I (CPT I), involved in the transport of long-chain fatty acyl goups into the mitochondria, medium-chain acyl-CoA dehydrogenase (involved in beta-oxidation) and, specifically in liver, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (the rate limiting enzyme of ketogenesis), peroxisomal acyl-CoA oxidase (peroxisomal beta-oxidation), and microsomal cytochrome P450 (CYP) FA omega-hydroxylases.
Formal Description
Interaction-ID: 4773

gene/protein

PPARA

affects_expression of

gene/protein

CPT1A

Drugbank entries Show/Hide entries for PPARA or CPT1A
Comment PPAR-alpha target genes include carnitine palmitoyltransferase I (CPT I), involved in the transport of long-chain fatty acyl goups into the mitochondria, medium-chain acyl-CoA dehydrogenase (involved in beta-oxidation) and, specifically in liver, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (the rate limiting enzyme of ketogenesis), peroxisomal acyl-CoA oxidase (peroxisomal beta-oxidation), and microsomal cytochrome P450 (CYP) FA omega-hydroxylases.
Formal Description
Interaction-ID: 4777

gene/protein

PPARA

affects_expression of

gene/protein

ACADM

Drugbank entries Show/Hide entries for PPARA or ACADM
Comment PPAR-alpha target genes include carnitine palmitoyltransferase I (CPT I), involved in the transport of long-chain fatty acyl goups into the mitochondria, medium-chain acyl-CoA dehydrogenase (involved in beta-oxidation) and, specifically in liver, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (the rate limiting enzyme of ketogenesis), peroxisomal acyl-CoA oxidase (peroxisomal beta-oxidation), and microsomal cytochrome P450 (CYP) FA omega-hydroxylases.
Formal Description
Interaction-ID: 4778

gene/protein

PPARA

affects_expression of

gene/protein

HMGCS2

in liver
Drugbank entries Show/Hide entries for PPARA
Comment PPAR-alpha target genes include carnitine palmitoyltransferase I (CPT I), involved in the transport of long-chain fatty acyl goups into the mitochondria, medium-chain acyl-CoA dehydrogenase (involved in beta-oxidation) and, specifically in liver, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (the rate limiting enzyme of ketogenesis), peroxisomal acyl-CoA oxidase (peroxisomal beta-oxidation), and microsomal cytochrome P450 (CYP) FA omega-hydroxylases.
Formal Description
Interaction-ID: 4780

gene/protein

PPARA

affects_expression of

gene/protein

ACOX

in liver
Drugbank entries Show/Hide entries for PPARA
Comment PPAR-alpha target genes include carnitine palmitoyltransferase I (CPT I), involved in the transport of long-chain fatty acyl goups into the mitochondria, medium-chain acyl-CoA dehydrogenase (involved in beta-oxidation) and, specifically in liver, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (the rate limiting enzyme of ketogenesis), peroxisomal acyl-CoA oxidase (peroxisomal beta-oxidation), and microsomal cytochrome P450 (CYP) FA omega-hydroxylases.
Formal Description
Interaction-ID: 4783

gene/protein

PPARA

affects_activity of

into mitochondria
Drugbank entries Show/Hide entries for PPARA
Comment PPAR-alpha target genes include carnitine palmitoyltransferase I (CPT I), involved in the transport of long-chain fatty acyl goups into the mitochondria, medium-chain acyl-CoA dehydrogenase (involved in beta-oxidation) and, specifically in liver, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (the rate limiting enzyme of ketogenesis), peroxisomal acyl-CoA oxidase (peroxisomal beta-oxidation), and microsomal cytochrome P450 (CYP) FA omega-hydroxylases.
Formal Description
Interaction-ID: 4784

gene/protein

PPARA

affects_activity of

Drugbank entries Show/Hide entries for PPARA
Comment PPAR-alpha target genes include carnitine palmitoyltransferase I (CPT I), involved in the transport of long-chain fatty acyl goups into the mitochondria, medium-chain acyl-CoA dehydrogenase (involved in beta-oxidation) and, specifically in liver, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (the rate limiting enzyme of ketogenesis), peroxisomal acyl-CoA oxidase (peroxisomal beta-oxidation), and microsomal cytochrome P450 (CYP) FA omega-hydroxylases.
Formal Description
Interaction-ID: 4785

gene/protein

PPARA

affects_activity of

in liver
Drugbank entries Show/Hide entries for PPARA
Comment PPAR-alpha plays a critical role in maintenance of lipid homeostasis (oxidation and production).
Formal Description
Interaction-ID: 4786

gene/protein

PPARA

affects_activity of

Drugbank entries Show/Hide entries for PPARA
Comment Exposure of insulin-sensitive tissues (in particular liver and skeletal muscle) to excess nonesterified fatty acids (FA) and circulating triglycerides (triacylglycerol, TAG) induces insulin resistance that can be corrected by the administration of PPAR-alpha activators by actions to promote removal of intracellular lipid through tissue FA oxidation.
Formal Description
Interaction-ID: 4787

gene/protein

PPARA

decreases_activity of

disease

Insulin resistance

in liver, in skeletal muscle; if induced by excess nonesterified fatty acids and circulating triacylglycerol
Drugbank entries Show/Hide entries for PPARA
Comment Induction of PPAR-alpha gene targets requires the interaction of PPAR-alpha and PGC-1, often in complex with other enzymes and coactivators.
Formal Description
Interaction-ID: 4788

gene/protein

PPARA

interacts (colocalizes) with

gene/protein

PPARGC1A

Drugbank entries Show/Hide entries for PPARA
Comment Lipin-1 induces PPAR-alpha gene expression as well as forming an interactive complex with PPAR-alpha and PGC-1alpha leading to induction of FA oxidation genes including CPT1.
Formal Description
Interaction-ID: 4894

gene/protein

LPIN1

increases_expression of

gene/protein

PPARA

in nucleus
Drugbank entries Show/Hide entries for PPARA
Comment The observation that, in liver, TRIB3 is a target for PPAR-alpha and that knockdown of hepatic TRIB3 expression improves glucose tolerance, whereas hepatic overexpression of TRIB3 reverses the insulin-sensitive phenotype of PGC-1-deficient mice has led to the suggestion that TRIB3 inhibitors may have a potential role in the treatment of T2DM. However, chronic reduction of hepatic PGC-1alpha expression has been shown to impair hepatic insulin sensitivity.
Formal Description
Interaction-ID: 5110

gene/protein

PPARA

affects_activity of

gene/protein

TRIB3

in liver
Drugbank entries Show/Hide entries for PPARA
Comment Overexpression in liver of the long form of lipin-1 (lipin-1beta, the predominant form in liver) increases the expression of PPAR-alpha and PPAR-alpha target genes involved in FA uptake and utilization.
Formal Description
Interaction-ID: 5126

mRNA/protein variant

LPIN1B

increases_expression of

gene/protein

PPARA

Drugbank entries Show/Hide entries for PPARA
Comment PGC-1 coactivators functionally interact with transcription factors, in particular with members of the NR superfamily such as PPAR-gamma and PPAR-alpha, ERR, LXR, and HNF-4alpha, but also with non-NR transcription factors and regulatory elements including cAMP response element-binding protein (CREB), the lipogenic transcription factor sterol regulatory element-binding protein-1c (SREBP-1c or SREBF1), and forkhead box O1 (FOXO1), abnormalities in which have been implicated in the development of diabetes.
Formal Description
Interaction-ID: 45968

gene/protein

PPARGC1

affects_activity of

gene/protein

PPARA

Drugbank entries Show/Hide entries for PPARA