General Information:

Id: 824
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 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: 4771

complex/PPI

PPARA-RXR complex

affects_activity of

if lipid-induced
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 SIRT1-mediated deacetylation activates PGC-1alpha, while acetylation by GCN5 inhibits PGC-1alpha-directed gene expression.
Formal Description
Interaction-ID: 4790

gene/protein

SIRT1

decreases_acetylation of

gene/protein

PPARGC1A

Comment SIRT1-mediated deacetylation activates PGC-1alpha, while acetylation by GCN5 inhibits PGC-1alpha-directed gene expression.
Formal Description
Interaction-ID: 4791

gene/protein

SIRT1

increases_activity of

gene/protein

PPARGC1A

Comment SIRT1-mediated deacetylation activates PGC-1alpha, while acetylation by GCN5 inhibits PGC-1alpha-directed gene expression.
Formal Description
Interaction-ID: 4792

gene/protein

KAT2A

increases_acetylation of

gene/protein

PPARGC1A

Drugbank entries Show/Hide entries for KAT2A
Comment SIRT1-mediated deacetylation activates PGC-1alpha, while acetylation by GCN5 inhibits PGC-1alpha-directed gene expression.
Formal Description
Interaction-ID: 4793

gene/protein

KAT2A

decreases_activity of

gene/protein

PPARGC1A

Drugbank entries Show/Hide entries for KAT2A
Comment In skeletal muscle, phosphorylation by AMPK and p38 MAPK increases stabilization of PGC-1alpha.
Formal Description
Interaction-ID: 4794

complex/PPI

AMPK

increases_phosphorylation of

gene/protein

PPARGC1A

in skeletal muscle
Comment In skeletal muscle, phosphorylation by AMPK and p38 MAPK increases stabilization of PGC-1alpha.
Formal Description
Interaction-ID: 4795

gene/protein

p38 MAPK

increases_phosphorylation of

gene/protein

PPARGC1A

in skeletal muscle
Comment In skeletal muscle, phosphorylation by AMPK and p38 MAPK increases stabilization of PGC-1alpha.
Formal Description
Interaction-ID: 4797

complex/PPI

AMPK

increases_quantity of

gene/protein

PPARGC1A

in skeletal muscle; via decreased degradation of PPARGC1A
Comment In skeletal muscle, phosphorylation by AMPK and p38 MAPK increases stabilization of PGC-1alpha.
Formal Description
Interaction-ID: 4799

gene/protein

p38 MAPK

increases_quantity of

gene/protein

PPARGC1A

in skeletal muscle; via decreased degradation of PPARGC1A
Comment AKT/PKB-mediated phosphorylation facilitates degradation of hepatic PGC-1alpha.
Formal Description
Interaction-ID: 4800

gene/protein

AKT1

increases_phosphorylation of

gene/protein

PPARGC1A

in liver
Drugbank entries Show/Hide entries for AKT1
Comment AKT/PKB-mediated phosphorylation facilitates degradation of hepatic PGC-1alpha.
Formal Description
Interaction-ID: 4802

gene/protein

AKT1

decreases_quantity of

gene/protein

PPARGC1A

in liver; via increased degradation of PPARGC1A
Drugbank entries Show/Hide entries for AKT1
Comment PRMT1 also activates PGC-1alpha through methylation at several arginine residues.
Formal Description
Interaction-ID: 4803

gene/protein

PRMT1

increases_methylation of

gene/protein

PPARGC1A

at several Arg residues
Drugbank entries Show/Hide entries for PRMT1
Comment PRMT1 also activates PGC-1alpha through methylation at several arginine residues.
Formal Description
Interaction-ID: 4804

gene/protein

PRMT1

increases_activity of

gene/protein

PPARGC1A

Drugbank entries Show/Hide entries for PRMT1
Comment The PGC-1s are a small family of transcriptional coactivators that play a critical role in the control of glucose, lipid, and energy metabolism. There are three known isoforms of PGC-1: PGC-1alpha (PPARGC1A); PGC-1beta (PPARGC1B); PGC-1-related coactivator (PRC or PPRC1).
Formal Description
Interaction-ID: 4805

gene/protein

PPARGC1A

affects_activity of

via regulation of a transcription factor
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: 4806

gene/protein

PPARGC1

affects_activity of

gene/protein

PPARG

Drugbank entries Show/Hide entries for PPARG
Comment HAT enzymes (histone acetyl transferases) such as p300, CBP, and SRC-1 bind to the amino terminal of PGC-1, where they function to acetylate and remodel chromatin, leading to modified access to target genes by transcriptional machinery.
Formal Description
Interaction-ID: 4807

gene/protein

EP300

interacts (colocalizes) with

gene/protein

PPARGC1

Comment HAT enzymes (histone acetyl transferases) such as p300, CBP, and SRC-1 bind to the amino terminal of PGC-1, where they function to acetylate and remodel chromatin, leading to modified access to target genes by transcriptional machinery.
Formal Description
Interaction-ID: 4808

gene/protein

CREBBP

interacts (colocalizes) with

gene/protein

PPARGC1

Drugbank entries Show/Hide entries for CREBBP
Comment HAT enzymes (histone acetyl transferases) such as p300, CBP, and SRC-1 bind to the amino terminal of PGC-1, where they function to acetylate and remodel chromatin, leading to modified access to target genes by transcriptional machinery.
Formal Description
Interaction-ID: 4809

gene/protein

NCOA1

interacts (colocalizes) with

gene/protein

PPARGC1

Drugbank entries Show/Hide entries for NCOA1
Comment HAT enzymes (histone acetyl transferases) such as p300, CBP, and SRC-1 bind to the amino terminal of PGC-1, where they function to acetylate and remodel chromatin, leading to modified access to target genes by transcriptional machinery.
Formal Description
Interaction-ID: 4810

complex/PPI

HAT-PPARGC1 complex

increases_acetylation of

complex/PPI

Chromatin

Comment HAT enzymes (histone acetyl transferases) such as p300, CBP, and SRC-1 bind to the amino terminal of PGC-1, where they function to acetylate and remodel chromatin, leading to modified access to target genes by transcriptional machinery.
Formal Description
Interaction-ID: 4811

complex/PPI

HAT-PPARGC1 complex

increases_activity of

Comment Both PGC-1alpha and PGC-1beta are found in complex with GCN5, an acetyl transferase which acetylates PGC-1 at several lysine residues and inhibits its transcriptional activity.
Formal Description
Interaction-ID: 4812

gene/protein

PPARGC1A

interacts (colocalizes) with

gene/protein

KAT2A

Drugbank entries Show/Hide entries for KAT2A
Comment Both PGC-1alpha and PGC-1beta are found in complex with GCN5, an acetyl transferase which acetylates PGC-1 at several lysine residues and inhibits its transcriptional activity.
Formal Description
Interaction-ID: 4813

gene/protein

PPARGC1B

interacts (colocalizes) with

gene/protein

KAT2A

Drugbank entries Show/Hide entries for KAT2A
Comment Both PGC-1alpha and PGC-1beta are found in complex with GCN5, an acetyl transferase which acetylates PGC-1 at several lysine residues and inhibits its transcriptional activity.
Formal Description
Interaction-ID: 4814

gene/protein

KAT2A

increases_acetylation of

gene/protein

PPARGC1B

Drugbank entries Show/Hide entries for KAT2A
Comment Both PGC-1alpha and PGC-1beta are found in complex with GCN5, an acetyl transferase which acetylates PGC-1 at several lysine residues and inhibits its transcriptional activity.
Formal Description
Interaction-ID: 4815

gene/protein

KAT2A

decreases_activity of

gene/protein

PPARGC1B

Drugbank entries Show/Hide entries for KAT2A
Comment Protein deacetylase SIRT1 (the mammalian Sir2 ortholog) deacetylates a number of nonhistone targets including PGC-1alpha and PGC-1beta, with activation of both cofactors.
Formal Description
Interaction-ID: 4816

gene/protein

SIRT1

decreases_acetylation of

gene/protein

PPARGC1B

Comment Protein deacetylase SIRT1 (the mammalian Sir2 ortholog) deacetylates a number of nonhistone targets including PGC-1alpha and PGC-1beta, with activation of both cofactors.
Formal Description
Interaction-ID: 4817

gene/protein

SIRT1

increases_activity of

gene/protein

PPARGC1B

Comment SIRT1, located in the cell nucleus, requires NAD(+) as a cofactor and is negatively regulated by either NADH or the deacetylation product nicotinamide.
Formal Description
Interaction-ID: 4818

gene/protein

SIRT1

is localized in

cellular component

nucleus

Comment Nonobese diabetic Goto-Kakizaki rats, a rodent model of diabetes, have decreased hepatic PRMT activity associated with impaired arginine methylation, and transfection with PRMT siRNA attenuates insulin signaling to gluconeogenic gene expression.
Formal Description
Interaction-ID: 4819

organism model

non-obese diabetic Goto-Kakizaki rat

decreases_activity of

gene/protein

PRMT1

in liver
Drugbank entries Show/Hide entries for PRMT1
Comment Expression of PGC-1 coactivators in the liver is relatively low in the fed state; however, in parallel with effects of fasting to increase PPAR-alpha signaling, hepatic PGC-1alpha mRNA expression is elevated after starvation and plays a critical role in the regulation of hepatic gluconeogenesis and fatty acid oxidation.
Formal Description
Interaction-ID: 4840

environment

fasting

increases_expression of

gene/protein

PPARGC1A

in liver
Comment Expression of PGC-1 coactivators in the liver is relatively low in the fed state; however, in parallel with effects of fasting to increase PPAR-alpha signaling, hepatic PGC-1alpha mRNA expression is elevated after starvation and plays a critical role in the regulation of hepatic gluconeogenesis and fatty acid oxidation.
Formal Description
Interaction-ID: 4841

gene/protein

PPARGC1A

affects_activity of

process

gluconeogenesis

in liver
Comment Expression of PGC-1 coactivators in the liver is relatively low in the fed state; however, in parallel with effects of fasting to increase PPAR-alpha signaling, hepatic PGC-1alpha mRNA expression is elevated after starvation and plays a critical role in the regulation of hepatic gluconeogenesis and fatty acid oxidation.
Formal Description
Interaction-ID: 4842

environment

fasting

increases_activity of

in liver
Comment Expression of PGC-1 coactivators in the liver is relatively low in the fed state; however, in parallel with effects of fasting to increase PPAR-alpha signaling, hepatic PGC-1alpha mRNA expression is elevated after starvation and plays a critical role in the regulation of hepatic gluconeogenesis and fatty acid oxidation.
Formal Description
Interaction-ID: 4843

gene/protein

PPARGC1A

affects_activity of

in liver
Comment Increased expression of PGC-1alpha in liver via adenovirus vector enhances hepatic glucose production.
Formal Description
Interaction-ID: 4844

gene/protein

PPARGC1A

increases_activity of

process

gluconeogenesis

in liver; if PPARGC1A is overexpressed
Comment The rise in glucagon levels on fasting is associated with the dephosphorylation and translocation of the CREB-regulated transcription coactivator (TORC2 or CRTC2) to the nucleus, where it coactivates CREB, a transcription factor present on the PGC-1alpha gene promoter, leading to induction of PGC-1alpha.
Formal Description
Interaction-ID: 4845

environment

fasting

increases_quantity of

gene/protein

Glucagon

in liver
Comment The rise in glucagon levels on fasting is associated with the dephosphorylation and translocation of the CREB-regulated transcription coactivator (TORC2 or CRTC2) to the nucleus, where it coactivates CREB, a transcription factor present on the PGC-1alpha gene promoter, leading to induction of PGC-1alpha.
Formal Description
Interaction-ID: 4847

gene/protein

Glucagon

decreases_phosphorylation of

gene/protein

CRTC2

in liver
Comment The rise in glucagon levels on fasting is associated with the dephosphorylation and translocation of the CREB-regulated transcription coactivator (TORC2 or CRTC2) to the nucleus, where it coactivates CREB, a transcription factor present on the PGC-1alpha gene promoter, leading to induction of PGC-1alpha.
Formal Description
Interaction-ID: 4849

gene/protein

CRTC2

increases_activity of

gene/protein

CREB1

in liver
Drugbank entries Show/Hide entries for CREB1
Comment The rise in glucagon levels on fasting is associated with the dephosphorylation and translocation of the CREB-regulated transcription coactivator (TORC2 or CRTC2) to the nucleus, where it coactivates CREB, a transcription factor present on the PGC-1alpha gene promoter, leading to induction of PGC-1alpha.
Formal Description
Interaction-ID: 4850

gene/protein

CREB1

increases_activity of

gene/protein

PPARGC1A

in liver
Drugbank entries Show/Hide entries for CREB1
Comment PGC-1alpha subsequently coactivates and forms complexes with FoxO1, the GR and HNF-4alpha, which (as well as PPAR-alpha) are essential for expression of the key gluconeogenic genes PCK1 and/or G6Pase.
Formal Description
Interaction-ID: 4852

gene/protein

PPARGC1A

increases_activity of

gene/protein

FOXO1

in liver
Comment PGC-1alpha subsequently coactivates and forms complexes with FoxO1, the GR and HNF-4alpha, which (as well as PPAR-alpha) are essential for expression of the key gluconeogenic genes PCK1 and/or G6Pase.
Formal Description
Interaction-ID: 4854

gene/protein

PPARGC1A

increases_activity of

gene/protein

NR3C1

in liver
Drugbank entries Show/Hide entries for NR3C1
Comment PGC-1alpha subsequently coactivates and forms complexes with FoxO1, the GR and HNF-4alpha, which (as well as PPAR-alpha) are essential for expression of the key gluconeogenic genes PCK1 and/or G6Pase.
Formal Description
Interaction-ID: 4855

gene/protein

PPARGC1A

increases_activity of

gene/protein

HNF4A

in liver
Drugbank entries Show/Hide entries for HNF4A
Comment PGC-1alpha subsequently coactivates and forms complexes with FoxO1, the GR and HNF-4alpha, which (as well as PPAR-alpha) are essential for expression of the key gluconeogenic genes PCK1 and/or G6Pase.
Formal Description
Interaction-ID: 4856

complex/PPI

PPARGC1A-NR3C1-FOXO1-HNF4A-PPARA complex

increases_expression of

gene/protein

G6PC

in liver
Comment PGC-1alpha subsequently coactivates and forms complexes with FoxO1, the GR and HNF-4alpha, which (as well as PPAR-alpha) are essential for expression of the key gluconeogenic genes PCK1 and/or G6Pase.
Formal Description
Interaction-ID: 4857

complex/PPI

PPARGC1A-NR3C1-FOXO1-HNF4A-PPARA complex

increases_expression of

gene/protein

PCK1

in liver
Drugbank entries Show/Hide entries for PCK1
Comment PGC-1alpha subsequently coactivates and forms complexes with FoxO1, the GR and HNF-4alpha, which (as well as PPAR-alpha) are essential for expression of the key gluconeogenic genes PCK1 and/or G6Pase.
Formal Description
Interaction-ID: 4858

gene/protein

G6PC

increases_activity of

process

gluconeogenesis

in liver
Comment PGC-1alpha subsequently coactivates and forms complexes with FoxO1, the GR and HNF-4alpha, which (as well as PPAR-alpha) are essential for expression of the key gluconeogenic genes PCK1 and/or G6Pase.
Formal Description
Interaction-ID: 4859

gene/protein

PCK1

increases_activity of

process

gluconeogenesis

in liver
Drugbank entries Show/Hide entries for PCK1
Comment Activation of AKT by insulin elicits phosphorylation of both TORC2 and PGC-1alpha leading to their degradation.
Formal Description
Interaction-ID: 4860

complex/PPI

Insulin

increases_activity of

gene/protein

AKT1

in liver
Drugbank entries Show/Hide entries for AKT1
Comment Activation of AKT by insulin elicits phosphorylation of both TORC2 and PGC-1alpha leading to their degradation.
Formal Description
Interaction-ID: 4861

gene/protein

AKT1

increases_phosphorylation of

gene/protein

CRTC2

in liver
Drugbank entries Show/Hide entries for AKT1
Comment Activation of AKT by insulin elicits phosphorylation of both TORC2 and PGC-1alpha leading to their degradation.
Formal Description
Interaction-ID: 4862

gene/protein

AKT1

increases_phosphorylation of

gene/protein

PPARGC1A

in liver
Drugbank entries Show/Hide entries for AKT1
Comment Activation of AKT by insulin elicits phosphorylation of both TORC2 and PGC-1alpha leading to their degradation.
Formal Description
Interaction-ID: 4863

gene/protein

AKT1

decreases_quantity of

gene/protein

CRTC2

in liver; via increased degradation of CRTC2
Drugbank entries Show/Hide entries for AKT1
Comment Activation of AKT by insulin elicits phosphorylation of both TORC2 and PGC-1alpha leading to their degradation.
Formal Description
Interaction-ID: 4864

gene/protein

AKT1

decreases_quantity of

gene/protein

PPARGC1A

in liver; via increased degradation of PPARGC1A
Drugbank entries Show/Hide entries for AKT1
Comment Activation of AKT by insulin elicits phosphorylation of both TORC2 and PGC-1alpha leading to their degradation.
Formal Description
Interaction-ID: 4866

gene/protein

AKT1

decreases_activity of

gene/protein

CRTC2

in liver
Drugbank entries Show/Hide entries for AKT1
Comment Activation of AKT by insulin elicits phosphorylation of both TORC2 and PGC-1alpha leading to their degradation.
Formal Description
Interaction-ID: 4867

gene/protein

AKT1

decreases_activity of

gene/protein

PPARGC1A

in liver
Drugbank entries Show/Hide entries for AKT1
Comment PGC-1alpha is deacetylated by SIRT1, induction of PGC-1alpha being associated with coactivation of FOXO1 and HNF-4alpha and induction of gluconeogenic gene expression, this pathway is not activated by classical gluconeogenic stimuli, including the GCs and glucagon, but this pathway is inhibited by GCN5.
Formal Description
Interaction-ID: 4868

gene/protein

KAT2A

decreases_activity of

process

gluconeogenesis

in liver
Drugbank entries Show/Hide entries for KAT2A
Comment PGC-1alpha target genes for fatty acid (FA) oxidation are induced in skeletal muscle by SIRT1 and inhibited by GCN5.
Formal Description
Interaction-ID: 4869

gene/protein

SIRT1

increases_activity of

gene/protein

PPARGC1A

in skeletal muscle
Comment PGC-1alpha target genes for fatty acid (FA) oxidation are induced in skeletal muscle by SIRT1 and inhibited by GCN5.
Formal Description
Interaction-ID: 4870

gene/protein

KAT2A

decreases_activity of

gene/protein

PPARGC1A

in skeletal muscle
Drugbank entries Show/Hide entries for KAT2A
Comment PGC-1alpha target genes for fatty acid (FA) oxidation are induced in skeletal muscle by SIRT1 and inhibited by GCN5.
Formal Description
Interaction-ID: 4871

gene/protein

PPARGC1A

increases_activity of

in skeletal muscle
Comment In the cytoplasm, lipin-1 promotes TAG accumulation and phospholipid synthesis by functioning as a Mg2+-dependent phosphatidate phosphatase (phosphatidic acid phosphatase-1 (PAP-1). PAP-1 converts phosphatidate to diacylglycerol (DAG), the immediate precursor of TAG and neutral phospholipids.
Formal Description
Interaction-ID: 4878

gene/protein

LPIN1

increases_activity of

in cytoplasm
Comment In the cytoplasm, lipin-1 promotes TAG accumulation and phospholipid synthesis by functioning as a Mg2+-dependent phosphatidate phosphatase (phosphatidic acid phosphatase-1 (PAP-1). PAP-1 converts phosphatidate to diacylglycerol (DAG), the immediate precursor of TAG and neutral phospholipids.
Formal Description
Interaction-ID: 4882

gene/protein

LPIN1

increases_activity of

in cytoplasm
Comment In the nucleus, lipin-1 acts as a transcriptional coativator linked to FA oxidation.
Formal Description
Interaction-ID: 4893

gene/protein

LPIN1

affects_activity of

in nucleus
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 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: 4895

complex/PPI

LPIN1-PPARA-PPARGC1A complex

increases_expression of

gene/protein

CPT1A

in nucleus
Drugbank entries Show/Hide entries for CPT1A
Comment The lipogenic transcription factor SREBP-1 is involved in the regulation of lipin-1 expression and lipin-1 protein is induced by sterol depletion.
Formal Description
Interaction-ID: 4896

gene/protein

SREBF1

affects_expression of

gene/protein

LPIN1

in nucleus
Comment Lipin-1 gene expression is induced by T0901317, an activating ligand for the LXR.
Formal Description
Interaction-ID: 4897

gene/protein

NR1H

increases_expression of

gene/protein

LPIN1

in nucleus
Comment Lipin-1 is induced by TORC2, a key coactivator of gluconeogenic gene expression, which leads to increased levels of DAG and consequent activation of protein kinase C. This, in turn, leads to inhibition of Akt signaling and insulin resistance.
Formal Description
Interaction-ID: 4898

gene/protein

CRTC2

increases_expression of

gene/protein

LPIN1

in nucleus
Comment Lipin-1 is induced by TORC2, a key coactivator of gluconeogenic gene expression, which leads to increased levels of DAG and consequent activation of protein kinase C. This, in turn, leads to inhibition of Akt signaling and insulin resistance.
Formal Description
Interaction-ID: 4899

gene/protein

LPIN1

increases_quantity of

drug/chemical compound

Diacylglycerol

Comment Lipin-1 is induced by TORC2, a key coactivator of gluconeogenic gene expression, which leads to increased levels of DAG and consequent activation of protein kinase C. This, in turn, leads to inhibition of Akt signaling and insulin resistance.
Formal Description
Interaction-ID: 4900

drug/chemical compound

Diacylglycerol

increases_activity of

gene/protein

Protein kinase C

Comment Lipin-1 is induced by TORC2, a key coactivator of gluconeogenic gene expression, which leads to increased levels of DAG and consequent activation of protein kinase C. This, in turn, leads to inhibition of Akt signaling and insulin resistance.
Formal Description
Interaction-ID: 4901

gene/protein

Protein kinase C

decreases_activity of

Comment Lipin-1 is induced by TORC2, a key coactivator of gluconeogenic gene expression, which leads to increased levels of DAG and consequent activation of protein kinase C. This, in turn, leads to inhibition of Akt signaling and insulin resistance.
Formal Description
Interaction-ID: 4902

decreases_activity of

disease

Insulin resistance

Comment TORC2 induces PGC-1alpha, while knockdown of lipin-1 decreases PGC-1alpha mRNA levels.
Formal Description
Interaction-ID: 4903

gene/protein

CRTC2

increases_expression of

gene/protein

PPARGC1A

Comment TORC2 induces PGC-1alpha, while knockdown of lipin-1 decreases PGC-1alpha mRNA levels.
Formal Description
Interaction-ID: 4904

gene/protein

LPIN1

increases_expression of

gene/protein

PPARGC1A

Comment SIRT1 has been reported to deacetylate TORC2 leading to its ubiquitin-mediated degradation and inhibition of gluconeogenic gene expression.
Formal Description
Interaction-ID: 4905

gene/protein

SIRT1

decreases_acetylation of

gene/protein

CRTC2

Comment SIRT1 has been reported to deacetylate TORC2 leading to its ubiquitin-mediated degradation and inhibition of gluconeogenic gene expression.
Formal Description
Interaction-ID: 4906

gene/protein

SIRT1

decreases_quantity of

gene/protein

CRTC2

via ubiquitin-mediated degradation of CRTC2
Comment SIRT1 has been reported to deacetylate TORC2 leading to its ubiquitin-mediated degradation and inhibition of gluconeogenic gene expression.
Formal Description
Interaction-ID: 4907

gene/protein

SIRT1

decreases_activity of

process

gluconeogenesis

Comment SIRT1 acts on targets in a signal-specific manner, deacetylating PGC-1alpha only in response to nutrient signaling but not glucagon.
Formal Description
Interaction-ID: 4908

gene/protein

Glucagon

NOT affects_activity of

gene/protein

SIRT1

Comment Normal pancreatic islets express both PGC-1alpha and SIRT1 at low levels. As in liver, fasting for 24 h increases PGC-1alpha mRNA expression in islets, an effect reversed by 24 h of refeeding.
Formal Description
Interaction-ID: 4909

environment

fasting

increases_expression of

gene/protein

PPARGC1A

in pancreas, in pancreatic islets
Comment PGC-1alpha mRNA and protein expression have been reported to be elevated in islets from animal models of diabetes, including the ob/ob mouse and ZDF rats.
Formal Description
Interaction-ID: 4910

increases_expression of

gene/protein

PPARGC1A

in pancreas, in pancreatic islets
Comment Overexpression of PGC-1alpha in islets substantially reduces the expression of the beta-cell glucose sensors for glucose-stimulated insulin secretion (GSIS), GLUT2, and glucokinase, and also impairs GSIS, suggesting it can precipitate beta-cell dysfunction.
Formal Description
Interaction-ID: 4911

gene/protein

PPARGC1A

decreases_expression of

gene/protein

SLC2A2

in pancreas, in pancreatic islets
Drugbank entries Show/Hide entries for SLC2A2
Comment Overexpression of PGC-1alpha in islets substantially reduces the expression of the beta-cell glucose sensors for glucose-stimulated insulin secretion (GSIS), GLUT2, and glucokinase, and also impairs GSIS, suggesting it can precipitate beta-cell dysfunction.
Formal Description
Interaction-ID: 4912

gene/protein

PPARGC1A

decreases_expression of

gene/protein

GCK

in pancreas, in pancreatic islets
Drugbank entries Show/Hide entries for GCK
Comment Chronic hyperlipidemia and hyperglycemia, which together cause adverse effects on beta-cell function via glucolipotoxicity, also affect PGC-1alpha gene expression.
Formal Description
Interaction-ID: 4913

phenotype

hyperlipidemia

affects_expression of

gene/protein

PPARGC1A

in pancreas, in pancreatic islets
Comment Chronic hyperlipidemia and hyperglycemia, which together cause adverse effects on beta-cell function via glucolipotoxicity, also affect PGC-1alpha gene expression.
Formal Description
Interaction-ID: 4914

phenotype

hyperglycemia

affects_expression of

gene/protein

PPARGC1A

in pancreas, in pancreatic islets
Comment GLP-1 increases islet PGC-1alpha mRNA expression which leads to repression of genes involved in beta-cell glucose sensing with a marked inhibition of GSIS.
Formal Description
Interaction-ID: 4915

increases_expression of

gene/protein

PPARGC1A

in pancreas, in pancreatic islets
Comment GLP-1 increases islet PGC-1alpha mRNA expression which leads to repression of genes involved in beta-cell glucose sensing with a marked inhibition of GSIS.
Formal Description
Interaction-ID: 4916

gene/protein

PPARGC1A

decreases_activity of

in pancreas, in pancreatic islets
Comment Increased SIRT1 expression specifically in pancreatic beta-cells, which would be predicted to induce PPAR-alpha signaling through deacetylation and induction of PGC-1alpha, improves glucose tolerance and enhances insulin secretion, in particular first-phase insulin secretion in response to glucose.
Formal Description
Interaction-ID: 4917

gene/protein

SIRT1

increases_activity of

in pancreas, in pancreatic islets
Comment Increased SIRT1 expression specifically in pancreatic beta-cells, which would be predicted to induce PPAR-alpha signaling through deacetylation and induction of PGC-1alpha, improves glucose tolerance and enhances insulin secretion, in particular first-phase insulin secretion in response to glucose.
Formal Description
Interaction-ID: 4918

gene/protein

SIRT1

increases_activity of

in pancreas, in pancreatic islets
Comment The expression of Ucp2 and the prolactin receptor gene (Prlr), both of which significantly influence beta-cell function, were downregulated by SIRT1 overexpression.
Formal Description
Interaction-ID: 4919

gene/protein

SIRT1

decreases_expression of

gene/protein

UCP2

in pancreas, in pancreatic islets
Comment The expression of Ucp2 and the prolactin receptor gene (Prlr), both of which significantly influence beta-cell function, were downregulated by SIRT1 overexpression.
Formal Description
Interaction-ID: 4920

gene/protein

SIRT1

decreases_expression of

gene/protein

PRLR

in pancreas, in pancreatic islets
Drugbank entries Show/Hide entries for PRLR
Comment LXRs alpha and beta, like the PPARs, are a second family of nutrient-responsive nuclear receptors that heterodimerize with RXR to influence gene expression. LXR-beta (NR1H2) is ubiquitously expressed. LXR-alpha (NR1H3) is abundant in liver and also in adipose tissue, intestine, kidney, and spleen.
Formal Description
Interaction-ID: 4921

gene/protein

NR1H2

affects_activity of

Drugbank entries Show/Hide entries for NR1H2
Comment As well as acting as sensors of cellular cholesterol and modulating the expression of genes concerned with cellular cholesterol handling, the LXRs enhance expression of genes involved in fatty acid biosynthesis and TAG secretion.
Formal Description
Interaction-ID: 4922

gene/protein

NR1H

affects_activity of

Comment As well as acting as sensors of cellular cholesterol and modulating the expression of genes concerned with cellular cholesterol handling, the LXRs enhance expression of genes involved in fatty acid biosynthesis and TAG secretion.
Formal Description
Interaction-ID: 4923

gene/protein

NR1H

affects_activity of

Comment As well as acting as sensors of cellular cholesterol and modulating the expression of genes concerned with cellular cholesterol handling, the LXRs enhance expression of genes involved in fatty acid biosynthesis and TAG secretion.
Formal Description
Interaction-ID: 4924

gene/protein

NR1H

affects_activity of

Comment As in liver, LXR activation in adipocytes stimulates lipid accumulation.
Formal Description
Interaction-ID: 4925

gene/protein

NR1H

increases_quantity of

drug/chemical compound

Triacylglycerol

in liver, in adipose tissue
Comment LXR-alpha gene expression is increased in adipose tissue from obese human subjects.
Formal Description
Interaction-ID: 4926

disease

Obesity

increases_expression of

gene/protein

NR1H3

in adipose tissue
Drugbank entries Show/Hide entries for NR1H3
Comment LXR increases the synthesis of FA and TAG by upregulating SREBP-1c.
Formal Description
Interaction-ID: 4933

gene/protein

NR1H

increases_expression of

mRNA/protein variant

SREBF1c

Comment A carbohydrate response element-binding protein (ChREBP or MLXIPL), a glucose-sensitive transcription factor that enhances hepatic conversion of excess carbohydrate to lipid, is a hepatic LXR target which stimulates lipogenic genes independent of SREBP-1c.
Formal Description
Interaction-ID: 4935

gene/protein

MLXIPL

increases_activity of

in liver; independent of SREBF1c
Comment LXRs are acetylated at Lys432 in LXR-alpha and Lys433 in LXR-beta, and deacetylation regulates LXR transcriptional activity.
Formal Description
Interaction-ID: 4950

affects_activity of

gene/protein

NR1H2

at Lys433
Drugbank entries Show/Hide entries for NR1H2
Comment SIRT1 deacetylates and thus positively regulates LXR.
Formal Description
Interaction-ID: 4951

gene/protein

SIRT1

decreases_acetylation of

gene/protein

NR1H

Comment SIRT1 deacetylates and thus positively regulates LXR.
Formal Description
Interaction-ID: 4952

gene/protein

SIRT1

increases_activity of

gene/protein

NR1H

Comment Adenoviral-mediated overexpression of hepatic PGC-1beta in rats leads to increased TAG synthesis and VLDL secretion and consequent hypertriglyceridemia and hypercholesterolemia.
Formal Description
Interaction-ID: 4953

gene/protein

PPARGC1B

increases_activity of

in liver
Comment Adenoviral-mediated overexpression of hepatic PGC-1beta in rats leads to increased TAG synthesis and VLDL secretion and consequent hypertriglyceridemia and hypercholesterolemia.
Formal Description
Interaction-ID: 4954

gene/protein

PPARGC1B

increases_activity of

process

VLDL secretion

in liver
Comment Adenoviral-mediated overexpression of hepatic PGC-1beta in rats leads to increased TAG synthesis and VLDL secretion and consequent hypertriglyceridemia and hypercholesterolemia.
Formal Description
Interaction-ID: 4955

gene/protein

PPARGC1B

increases_activity of

Comment Adenoviral-mediated overexpression of hepatic PGC-1beta in rats leads to increased TAG synthesis and VLDL secretion and consequent hypertriglyceridemia and hypercholesterolemia.
Formal Description
Interaction-ID: 4957

gene/protein

PPARGC1B

increases_activity of

Comment PGC-1beta induces hepatic lipogenesis through coactivation of both LXR and SREBP-1.
Formal Description
Interaction-ID: 4959

gene/protein

PPARGC1B

increases_activity of

gene/protein

NR1H

in liver
Comment PGC-1beta induces hepatic lipogenesis through coactivation of both LXR and SREBP-1.
Formal Description
Interaction-ID: 4960

gene/protein

PPARGC1B

increases_activity of

gene/protein

SREBF1

in liver
Comment PGC-1beta is induced in liver in response to high dietary saturated fat and fructose.
Formal Description
Interaction-ID: 4961

environment

high-saturated-fat and fructose diet

increases_expression of

gene/protein

PPARGC1B

Comment PGC-1beta coactivates SREBP-1c and increases the expression of genes involved in the synthesis of FA, TAG and cholesterol, including FAS, SCD-1, HMG-CoA reductase, DGAT and GPAT.
Formal Description
Interaction-ID: 4962

complex/PPI

PPARGC1B-SREBF1c complex

increases_expression of

gene/protein

FASN

Drugbank entries Show/Hide entries for FASN
Comment PGC-1beta coactivates SREBP-1c and increases the expression of genes involved in the synthesis of FA, TAG and cholesterol, including FAS, SCD-1, HMG-CoA reductase, DGAT and GPAT.
Formal Description
Interaction-ID: 4964

complex/PPI

PPARGC1B-SREBF1c complex

increases_expression of

gene/protein

SCD

Comment PGC-1beta coactivates SREBP-1c and increases the expression of genes involved in the synthesis of FA, TAG and cholesterol, including FAS, SCD-1, HMG-CoA reductase, DGAT and GPAT.
Formal Description
Interaction-ID: 4965

complex/PPI

PPARGC1B-SREBF1c complex

increases_expression of

gene/protein

HMGCR

Drugbank entries Show/Hide entries for HMGCR
Comment PGC-1beta coactivates SREBP-1c and increases the expression of genes involved in the synthesis of FA, TAG and cholesterol, including FAS, SCD-1, HMG-CoA reductase, DGAT and GPAT.
Formal Description
Interaction-ID: 4966

complex/PPI

PPARGC1B-SREBF1c complex

increases_expression of

gene/protein

DGAT

Comment PGC-1beta coactivates SREBP-1c and increases the expression of genes involved in the synthesis of FA, TAG and cholesterol, including FAS, SCD-1, HMG-CoA reductase, DGAT and GPAT.
Formal Description
Interaction-ID: 4967

complex/PPI

PPARGC1B-SREBF1c complex

increases_expression of

gene/protein

GPAT

Comment Both PGC-1beta and SREBP-1c, but not PGC-1alpha, are induced in liver in response to acute (24-48 h) high (58%) dietary saturated fat (mainly hydrogenated coconut oil), the increases in PGC-1beta and SREBP-1c in response to dietary saturated fat were specific to liver and not replicated in skeletal muscle or white adipose tissue, while dietary cholesterol intake had little impact on hepatic PGC-1beta expression.
Formal Description
Interaction-ID: 4968

environment

high-saturated-fat diet

increases_expression of

gene/protein

PPARGC1B

in liver
Comment Both PGC-1beta and SREBP-1c, but not PGC-1alpha, are induced in liver in response to acute (24-48 h) high (58%) dietary saturated fat (mainly hydrogenated coconut oil), the increases in PGC-1beta and SREBP-1c in response to dietary saturated fat were specific to liver and not replicated in skeletal muscle or white adipose tissue, while dietary cholesterol intake had little impact on hepatic PGC-1beta expression.
Formal Description
Interaction-ID: 4969

environment

high-saturated-fat diet

increases_expression of

mRNA/protein variant

SREBF1c

in liver
Comment Both PGC-1beta and SREBP-1c, but not PGC-1alpha, are induced in liver in response to acute (24-48 h) high (58%) dietary saturated fat (mainly hydrogenated coconut oil), the increases in PGC-1beta and SREBP-1c in response to dietary saturated fat were specific to liver and not replicated in skeletal muscle or white adipose tissue, while dietary cholesterol intake had little impact on hepatic PGC-1beta expression.
Formal Description
Interaction-ID: 4970

environment

high-saturated-fat diet

NOT increases_expression of

gene/protein

PPARGC1A

Comment Both PGC-1beta and SREBP-1c, but not PGC-1alpha, are induced in liver in response to acute (24-48 h) high (58%) dietary saturated fat (mainly hydrogenated coconut oil), the increases in PGC-1beta and SREBP-1c in response to dietary saturated fat were specific to liver and not replicated in skeletal muscle or white adipose tissue, while dietary cholesterol intake had little impact on hepatic PGC-1beta expression.
Formal Description
Interaction-ID: 4995

environment

dietary cholesterol

NOT affects_expression of

gene/protein

PPARGC1B

Comment While SREBP overexpression alone increases lipogenic gene expression and heptic lipid levels, hypertriglyceridemia does not occur, probably as a result of parallel upregulation of hepatic low-density lipoprotein receptor (LDLR) levels. In contrast, PGC-1beta fails to stimulate LDLR expression, but does stimulate VLDL secretion, possibly via augmenting activation of LXRalpha, leading to hypertriglyceridemia and accumulation of cholesterol in VLDL, the precursor to LDL cholesterol.
Formal Description
Interaction-ID: 4997

gene/protein

SREBF

affects_activity of

if SREBF is overexpressed
Comment PPAR-gamma activation promotes lipid synthesis and storage in white adipose tisue, as well as preadipocyte differentiation to mature adipocytes.
Formal Description
Interaction-ID: 5002

gene/protein

PPARG

increases_activity of

in white adipose tissue
Drugbank entries Show/Hide entries for PPARG
Comment PPAR-gamma activation promotes lipid synthesis and storage in white adipose tisue, as well as preadipocyte differentiation to mature adipocytes.
Formal Description
Interaction-ID: 5004

gene/protein

PPARG

increases_activity of

process

lipid storage

in white adipose tissue
Drugbank entries Show/Hide entries for PPARG
Comment PPAR-gamma activation promotes lipid synthesis and storage in white adipose tisue, as well as preadipocyte differentiation to mature adipocytes.
Formal Description
Interaction-ID: 5005

gene/protein

PPARG

increases_activity of

in white adipose tissue
Drugbank entries Show/Hide entries for PPARG
Comment Wnt/beta-catenin signaling maintains preadipocytes in an undifferentiated state in part through inhibition of PPAR-gamma.
Formal Description
Interaction-ID: 5007

decreases_activity of

Comment Wnt/beta-catenin signaling maintains preadipocytes in an undifferentiated state in part through inhibition of PPAR-gamma.
Formal Description
Interaction-ID: 5010

decreases_activity of

gene/protein

PPARG

Drugbank entries Show/Hide entries for PPARG
Comment Rev-erb-alpha acts downstream of PPAR-gamma by facilitating gene expression of PPAR-gamma target genes, including that encoding C/EBP-alpha (important for the acquisition of insulin sensitivity) and acts as a repressor of anti-adipogenic genes.
Formal Description
Interaction-ID: 5015

gene/protein

NR1D1

increases_activity of

gene/protein

PPARG

Drugbank entries Show/Hide entries for PPARG
Comment Rev-erb-alpha acts downstream of PPAR-gamma by facilitating gene expression of PPAR-gamma target genes, including that encoding C/EBP-alpha (important for the acquisition of insulin sensitivity) and acts as a repressor of anti-adipogenic genes.
Formal Description
Interaction-ID: 5018

gene/protein

NR1D1

increases_expression of

gene/protein

CEBPA

Comment PPAR-delta, also expressed in adipose tissue, is not involved in preadipocyte differentiation directly, but is implicated in the control of preadipocyte proliferation and PPAR-gamma gene expression.
Formal Description
Interaction-ID: 5021

gene/protein

PPARD

affects_activity of

Drugbank entries Show/Hide entries for PPARD
Comment PPAR-delta, also expressed in adipose tissue, is not involved in preadipocyte differentiation directly, but is implicated in the control of preadipocyte proliferation and PPAR-gamma gene expression.
Formal Description
Interaction-ID: 5024

gene/protein

PPARD

affects_expression of

gene/protein

PPARG

Drugbank entries Show/Hide entries for PPARD or PPARG
Comment Certain PPAR-gamma target genes that are normally expressed only at low levels in mature adipocytes are dramatically upregulated by thiazolidinediones (TZDs), among these the enzyme glycerol kinase. Glycerol kinase allows glycerol 3-phosphate production from glycerol, thereby enhancing the capacity for FA esterification to TAG.
Formal Description
Interaction-ID: 5026

drug/chemical compound

Thiazolidinedione

increases_expression of

gene/protein

GK

Comment Unlike classic PPAR-gamma-target genes such as aP2 (which is constitutively associated with coactivators), the glycerol kinase gene is targeted by NR corepressors. TZDs trigger the dismissal of corepressor HDAC complexes and the recruitment of coactivators to the glycerol kinase gene. They also induce PGC-1alpha, whose recruitment to the glycerol kinase gene is sufficient to release the corepressors.
Formal Description
Interaction-ID: 5031

drug/chemical compound

Thiazolidinedione

affects_activity of

gene/protein

GK

Comment Ectopic expression of PGC-1alpha in white adipocytes increases the expression of UCP1, genes encoding respiratory chain proteins (cytochrome c-oxidase subunits COX II and IV) and enzymes of FA oxidation and causes white adipocytes to acquire features of brown adipocytes.
Formal Description
Interaction-ID: 5035

gene/protein

PPARGC1A

affects_expression of

gene/protein

UCP1

Comment In ob/ob mice, the expression of transcripts encoding mitochondrial proteins decreases with the development of obesity. TZD treatment in ob/ob mice increases PGC-1alpha expression and increases mitochondrial mass and energy expenditure.
Formal Description
Interaction-ID: 5041

drug/chemical compound

Thiazolidinedione

increases_expression of

gene/protein

PPARGC1A

Comment In mature adipocytes, SIRT1 binds and represses PPAR-gamma in association with mobilization of fat stores during food deprivation.
Formal Description
Interaction-ID: 5076

gene/protein

SIRT1

interacts (colocalizes) with

gene/protein

PPARG

in adipose tissue, in mature adipocytes
Drugbank entries Show/Hide entries for PPARG
Comment In mature adipocytes, SIRT1 binds and represses PPAR-gamma in association with mobilization of fat stores during food deprivation.
Formal Description
Interaction-ID: 5078

gene/protein

SIRT1

decreases_activity of

gene/protein

PPARG

in adipose tissue, in mature adipocytes
Drugbank entries Show/Hide entries for PPARG
Comment In mature adipocytes, SIRT1 binds and represses PPAR-gamma in association with mobilization of fat stores during food deprivation.
Formal Description
Interaction-ID: 5080

gene/protein

SIRT1

increases_activity of

process

fat reserve metabolic process

in adipose tissue, in mature adipocytes; during food deprivation
Comment Lipin-1 promotes adipocyte TAG storage, it physically interacts with PPAR-gamma and is recruited to PPAR-gamma response element upstream of the PEP carboxykinase (PEPCK) gene. PEPCK is involved in glycerogenesis in white adipose tissue.
Formal Description
Interaction-ID: 5082

gene/protein

LPIN1

interacts (colocalizes) with

gene/protein

PPARG

in white adipose tissue
Drugbank entries Show/Hide entries for PPARG
Comment Lipin-1 promotes adipocyte TAG storage, it physically interacts with PPAR-gamma and is recruited to PPAR-gamma response element upstream of the PEP carboxykinase (PEPCK) gene. PEPCK is involved in glycerogenesis in white adipose tissue.
Formal Description
Interaction-ID: 5083

gene/protein

LPIN1

increases_activity of

in white adipose tissue
Comment Lipin-1 promotes adipocyte TAG storage, it physically interacts with PPAR-gamma and is recruited to PPAR-gamma response element upstream of the PEP carboxykinase (PEPCK) gene. PEPCK is involved in glycerogenesis in white adipose tissue.
Formal Description
Interaction-ID: 5088

gene/protein

LPIN1

increases_activity of

gene/protein

PCK1

in white adipose tissue
Drugbank entries Show/Hide entries for PCK1
Comment Lipin-1 overexpression in adipocytes promotes increased TAG content and obesity.
Formal Description
Interaction-ID: 5089

gene/protein

LPIN1

increases_activity of

disease

Obesity

Comment Lipin-1 overexpression in adipocytes promotes increased TAG content and obesity.
Formal Description
Interaction-ID: 5090

gene/protein

LPIN1

increases_quantity of

drug/chemical compound

Triacylglycerol

in adipose tissue
Comment In the mouse, lipin-1 deficiency is associated with insulin resistance, whereas transgenic overexpression of lipin-1 in adipose tissue promotes insulin sensitivity, even though the mice have increased adiposity.
Formal Description
Interaction-ID: 5091

gene/protein

LPIN1

decreases_activity of

disease

Insulin resistance

Comment Hepatic PGC-1alpha is increased in rodent models of type 2 diabetes mellitus (T2DM) which may lead to induction of gluconeogenesis and hyperglycemia, while at least two clinical studies have identified a correlation between mutations of the PPARGC1A gene (previously known as the PGC-1alpha gene) and insulin resistance or diabetes.
Formal Description
Interaction-ID: 5092

gene/protein

PPARGC1A

affects_activity of

Comment Hepatic PGC-1alpha is increased in rodent models of type 2 diabetes mellitus (T2DM) which may lead to induction of gluconeogenesis and hyperglycemia, while at least two clinical studies have identified a correlation between mutations of the PPARGC1A gene (previously known as the PGC-1alpha gene) and insulin resistance or diabetes.
Formal Description
Interaction-ID: 5104

gene/protein

PPARGC1A

affects_activity of

disease

Insulin resistance

Comment Overexpression of PGC-1alpha in cultures of primary rat skeletal muscle cells induces increased expression of the mammalian tribbles homolog TRB3, an inhibitor of AKT signaling, highlighting the potential of PGC-1alpha to cause insulin resistance.
Formal Description
Interaction-ID: 5105

gene/protein

PPARGC1A

increases_expression of

gene/protein

TRIB3

in skeletal muscle
Comment Overexpression of PGC-1alpha in cultures of primary rat skeletal muscle cells induces increased expression of the mammalian tribbles homolog TRB3, an inhibitor of AKT signaling, highlighting the potential of PGC-1alpha to cause insulin resistance.
Formal Description
Interaction-ID: 5107

gene/protein

TRIB3

decreases_activity of

in skeletal muscle
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 Epigenetic modification, including DNA methylation, represents a molecular mechanism linking environmental events to altered gene expression and the development of disease states, including T2DM.
Formal Description
Interaction-ID: 5112
Comment A study undertook a genome-wide promoter analysis of DNA methylation, screening for genes differentially methylated in T2DM, which identified cytosine hypermethylation of PGC-1alpha in diabetic subjects. Hypermethylation of the PGC-1alpha promoter was associated with reduced PGC-1alpha expression.
Formal Description
Interaction-ID: 5125

decreases_expression of

gene/protein

PPARGC1A

via hypermethylation of the PPARGC1A promoter
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