General Information:

Id: 947 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Fatty liver disease, nonalcoholic
Insulin resistance
Mus musculus
SIRT1 LKO: liver-specific SIRT1 knockout mouse on the C57BL/6 background
article
Reference: Purushotham A et al.(2009) Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation Cell Metab. 4: 327-338 [PMID: 19356714]

Interaction Information:

Comment SIRT1 directly regulates PPAR-alpha transactivation.
Formal Description
Interaction-ID: 5780

gene/protein

SIRT1

increases_activity of

gene/protein

PPARA

Drugbank entries Show/Hide entries for PPARA
Comment SIRT1 interacts with PPAR-alpha and is required for the activation of PGC-1alpha.
Formal Description
Interaction-ID: 5787

gene/protein

SIRT1

interacts (colocalizes) with

gene/protein

PPARA

Drugbank entries Show/Hide entries for PPARA
Comment Activation of PPAR-alpha by fasting promotes lipolysis in white adipose tissues and stimulates fatty acid oxidation and ketogenesis in the liver.
Formal Description
Interaction-ID: 5789

environment

fasting

increases_activity of

gene/protein

PPARA

Drugbank entries Show/Hide entries for PPARA
Comment Activation of PPAR-alpha by fasting promotes lipolysis in white adipose tissues and stimulates fatty acid oxidation and ketogenesis in the liver.
Formal Description
Interaction-ID: 5790

gene/protein

PPARA

increases_activity of

in white adipose tissue
Drugbank entries Show/Hide entries for PPARA
Comment Activation of PPAR-alpha by fasting promotes lipolysis in white adipose tissues and stimulates fatty acid oxidation and ketogenesis in the liver.
Formal Description
Interaction-ID: 5791

gene/protein

PPARA

increases_activity of

in liver
Drugbank entries Show/Hide entries for PPARA
Comment Activation of PPAR-alpha by fasting promotes lipolysis in white adipose tissues and stimulates fatty acid oxidation and ketogenesis in the liver.
Formal Description
Interaction-ID: 5792

gene/protein

PPARA

increases_activity of

in liver
Drugbank entries Show/Hide entries for PPARA
Comment Levels of PPAR-alpha targets known to regulate fatty acid oxidation were significantly lower in SIRT1 LKO mouse livers upon high-fat diet feeding: CPT1a, CPT2, ACAD, AOX, CD36, Cyp4A14, and Cyp4A10.
Formal Description
Interaction-ID: 5812

gene/protein

PPARA

increases_expression of

gene/protein

CPT1A

Drugbank entries Show/Hide entries for PPARA or CPT1A
Comment Levels of PPAR-alpha targets known to regulate fatty acid oxidation were significantly lower in SIRT1 LKO mouse livers upon high-fat diet feeding: CPT1a, CPT2, ACAD, AOX, CD36, Cyp4A14, and Cyp4A10.
Formal Description
Interaction-ID: 5814

gene/protein

PPARA

increases_expression of

gene/protein

CPT2

Drugbank entries Show/Hide entries for PPARA or CPT2
Comment Levels of PPAR-alpha targets known to regulate fatty acid oxidation were significantly lower in SIRT1 LKO mouse livers upon high-fat diet feeding: CPT1a, CPT2, ACAD, AOX, CD36, Cyp4A14, and Cyp4A10.
Formal Description
Interaction-ID: 5815

gene/protein

PPARA

increases_expression of

gene/protein

ACAD

Drugbank entries Show/Hide entries for PPARA
Comment Levels of PPAR-alpha targets known to regulate fatty acid oxidation were significantly lower in SIRT1 LKO mouse livers upon high-fat diet feeding: CPT1a, CPT2, ACAD, AOX, CD36, Cyp4A14, and Cyp4A10.
Formal Description
Interaction-ID: 5816

gene/protein

PPARA

increases_expression of

gene/protein

ACOX1

Drugbank entries Show/Hide entries for PPARA or ACOX1
Comment Levels of PPAR-alpha targets known to regulate fatty acid oxidation were significantly lower in SIRT1 LKO mouse livers upon high-fat diet feeding: CPT1a, CPT2, ACAD, AOX, CD36, Cyp4A14, and Cyp4A10.
Formal Description
Interaction-ID: 5817

gene/protein

PPARA

increases_expression of

gene/protein

CD36

Drugbank entries Show/Hide entries for PPARA
Comment Levels of PPAR-alpha targets known to regulate fatty acid oxidation were significantly lower in SIRT1 LKO mouse livers upon high-fat diet feeding: CPT1a, CPT2, ACAD, AOX, CD36, Cyp4A14, and Cyp4A10.
Formal Description
Interaction-ID: 5818

gene/protein

PPARA

increases_expression of

gene/protein

Cyp4A14

Drugbank entries Show/Hide entries for PPARA
Comment Levels of PPAR-alpha targets known to regulate fatty acid oxidation were significantly lower in SIRT1 LKO mouse livers upon high-fat diet feeding: CPT1a, CPT2, ACAD, AOX, CD36, Cyp4A14, and Cyp4A10.
Formal Description
Interaction-ID: 5819

gene/protein

PPARA

increases_expression of

gene/protein

Cyp4A10

Drugbank entries Show/Hide entries for PPARA
Comment Upon high-fat diet feeding a reduction in the expression of mitochondrial oxidative phosphorylation genes (Cytochrome C, Cox4 and Cox5b) was observed in livers of SIRT1 LKO mice. The decreased expression of the above-mentioned PPAR-alpha target genes was accompanied by a 40% decrease in the expression of PGC-1alpha mRNA.
Formal Description
Interaction-ID: 5844

gene/protein

PPARA

increases_expression of

gene/protein

CYCS

Drugbank entries Show/Hide entries for PPARA or CYCS
Comment Upon high-fat diet feeding a reduction in the expression of mitochondrial oxidative phosphorylation genes (Cytochrome C, Cox4 and Cox5b) was observed in livers of SIRT1 LKO mice. The decreased expression of the above-mentioned PPAR-alpha target genes was accompanied by a 40% decrease in the expression of PGC-1alpha mRNA.
Formal Description
Interaction-ID: 5845

gene/protein

PPARA

increases_expression of

gene/protein

COX4

Drugbank entries Show/Hide entries for PPARA
Comment Upon high-fat diet feeding a reduction in the expression of mitochondrial oxidative phosphorylation genes (Cytochrome C, Cox4 and Cox5b) was observed in livers of SIRT1 LKO mice. The decreased expression of the above-mentioned PPAR-alpha target genes was accompanied by a 40% decrease in the expression of PGC-1alpha mRNA.
Formal Description
Interaction-ID: 5847

gene/protein

PPARA

increases_expression of

gene/protein

COX5B

Drugbank entries Show/Hide entries for PPARA or COX5B
Comment To elucidate the regulatory role of SIRT1 in PPAR-alpha signaling in liver, primary hepatocytes from Lox control or SIRT1 LKO mice were treated with a PPAR-alpha agonist WY14643. WY treatment induced the expression of several genes involved in fatty acid oxidation in control hepatocytes. However, the induction of these genes was significantly lower in the SIRT1 deficient (LKO) hepatocytes.
Formal Description
Interaction-ID: 13194

gene/protein

PPARA

increases_activity of

in liver
Drugbank entries Show/Hide entries for PPARA