General Information:

Id: 947
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 Hepatic deletion of SIRT1 alters PPAR-alpha signaling.
Formal Description
Interaction-ID: 5731

gene/protein

SIRT1

affects_activity of

process

peroxisome proliferator activated receptor alpha signaling pathway

in liver; if SIRT1 is knocked out in liver
Comment Quantitative real-time PCR (qPCR) confirmed decreased expression of several PPAR-alpha targets, including medium chain acyl-CoA dehydrogenase (MCAD), liver bifunctional enzyme (Ehhadh), palmitoyl acyl-CoA carboxylase (AOX), fatty acid transporter (CD36), and microsomal cytochrome P450 enzymes involved in the omega-oxidation of fatty acids (Cyp4A10 and Cyp4A14), in SIRT1 LKO mice compared to Lox controls. In contrast, the mRNA level of SPOT14, a gene known to be negatively regulated by PPAR-alpha, was significantly higher in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 5742

gene/protein

SIRT1

affects_expression of

gene/protein

ACADM

in liver; on chow diet, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for ACADM
Comment Quantitative real-time PCR (qPCR) confirmed decreased expression of several PPAR-alpha targets, including medium chain acyl-CoA dehydrogenase (MCAD), liver bifunctional enzyme (Ehhadh), palmitoyl acyl-CoA carboxylase (AOX), fatty acid transporter (CD36), and microsomal cytochrome P450 enzymes involved in the omega-oxidation of fatty acids (Cyp4A10 and Cyp4A14), in SIRT1 LKO mice compared to Lox controls. In contrast, the mRNA level of SPOT14, a gene known to be negatively regulated by PPAR-alpha, was significantly higher in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 5746

gene/protein

SIRT1

affects_expression of

gene/protein

EHHADH

in liver; on chow diet, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for EHHADH
Comment Quantitative real-time PCR (qPCR) confirmed decreased expression of several PPAR-alpha targets, including medium chain acyl-CoA dehydrogenase (MCAD), liver bifunctional enzyme (Ehhadh), palmitoyl acyl-CoA carboxylase (AOX), fatty acid transporter (CD36), and microsomal cytochrome P450 enzymes involved in the omega-oxidation of fatty acids (Cyp4A10 and Cyp4A14), in SIRT1 LKO mice compared to Lox controls. In contrast, the mRNA level of SPOT14, a gene known to be negatively regulated by PPAR-alpha, was significantly higher in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 5747

gene/protein

SIRT1

affects_expression of

gene/protein

ACOX1

in liver; on chow diet, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for ACOX1
Comment Quantitative real-time PCR (qPCR) confirmed decreased expression of several PPAR-alpha targets, including medium chain acyl-CoA dehydrogenase (MCAD), liver bifunctional enzyme (Ehhadh), palmitoyl acyl-CoA carboxylase (AOX), fatty acid transporter (CD36), and microsomal cytochrome P450 enzymes involved in the omega-oxidation of fatty acids (Cyp4A10 and Cyp4A14), in SIRT1 LKO mice compared to Lox controls. In contrast, the mRNA level of SPOT14, a gene known to be negatively regulated by PPAR-alpha, was significantly higher in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 5754

gene/protein

SIRT1

affects_expression of

gene/protein

CD36

in liver; on chow diet, if SIRT1 is knocked out in liver
Comment Quantitative real-time PCR (qPCR) confirmed decreased expression of several PPAR-alpha targets, including medium chain acyl-CoA dehydrogenase (MCAD), liver bifunctional enzyme (Ehhadh), palmitoyl acyl-CoA carboxylase (AOX), fatty acid transporter (CD36), and microsomal cytochrome P450 enzymes involved in the omega-oxidation of fatty acids (Cyp4A10 and Cyp4A14), in SIRT1 LKO mice compared to Lox controls. In contrast, the mRNA level of SPOT14, a gene known to be negatively regulated by PPAR-alpha, was significantly higher in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 5755

gene/protein

SIRT1

affects_expression of

gene/protein

Cyp4A10

in liver; on chow diet, if SIRT1 is knocked out in liver
Comment Quantitative real-time PCR (qPCR) confirmed decreased expression of several PPAR-alpha targets, including medium chain acyl-CoA dehydrogenase (MCAD), liver bifunctional enzyme (Ehhadh), palmitoyl acyl-CoA carboxylase (AOX), fatty acid transporter (CD36), and microsomal cytochrome P450 enzymes involved in the omega-oxidation of fatty acids (Cyp4A10 and Cyp4A14), in SIRT1 LKO mice compared to Lox controls. In contrast, the mRNA level of SPOT14, a gene known to be negatively regulated by PPAR-alpha, was significantly higher in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 5756

gene/protein

SIRT1

affects_expression of

gene/protein

Cyp4A14

in liver; on chow diet, if SIRT1 is knocked out in liver
Comment Quantitative real-time PCR (qPCR) confirmed decreased expression of several PPAR-alpha targets, including medium chain acyl-CoA dehydrogenase (MCAD), liver bifunctional enzyme (Ehhadh), palmitoyl acyl-CoA carboxylase (AOX), fatty acid transporter (CD36), and microsomal cytochrome P450 enzymes involved in the omega-oxidation of fatty acids (Cyp4A10 and Cyp4A14), in SIRT1 LKO mice compared to Lox controls. In contrast, the mRNA level of SPOT14, a gene known to be negatively regulated by PPAR-alpha, was significantly higher in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 5758

gene/protein

SIRT1

affects_expression of

gene/protein

THRSP

in liver; on chow diet, if SIRT1 is knocked out in liver
Comment SIRT1 LKO mice displayed reduced expression of several PPAR-alpha target genes after overnight fasting: CPT1a, AOX, CD36, Cyp4A14, CytoC, and PGC-1a. Interestingly, the expression of PPAR-gamma co-activator 1-alpha (PGC-1alpha), a transcription co-factor known to activate PPAR-alpha, was also significantly lower in SIRT1 LKO mice.
Formal Description
Interaction-ID: 5759

gene/protein

SIRT1

affects_expression of

gene/protein

CPT1A

in liver; after overnight fasting, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for CPT1A
Comment SIRT1 LKO mice displayed reduced expression of several PPAR-alpha target genes after overnight fasting: CPT1a, AOX, CD36, Cyp4A14, CytoC, and PGC-1a. Interestingly, the expression of PPAR-gamma co-activator 1-alpha (PGC-1alpha), a transcription co-factor known to activate PPAR-alpha, was also significantly lower in SIRT1 LKO mice.
Formal Description
Interaction-ID: 5763

gene/protein

SIRT1

affects_expression of

gene/protein

ACOX1

in liver; after overnight fasting, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for ACOX1
Comment SIRT1 LKO mice displayed reduced expression of several PPAR-alpha target genes after overnight fasting: CPT1a, AOX, CD36, Cyp4A14, CytoC, and PGC-1a. Interestingly, the expression of PPAR-gamma co-activator 1-alpha (PGC-1alpha), a transcription co-factor known to activate PPAR-alpha, was also significantly lower in SIRT1 LKO mice.
Formal Description
Interaction-ID: 5764

gene/protein

SIRT1

affects_expression of

gene/protein

CD36

in liver; after overnight fasting, if SIRT1 is knocked out in liver
Comment SIRT1 LKO mice displayed reduced expression of several PPAR-alpha target genes after overnight fasting: CPT1a, AOX, CD36, Cyp4A14, CytoC, and PGC-1a. Interestingly, the expression of PPAR-gamma co-activator 1-alpha (PGC-1alpha), a transcription co-factor known to activate PPAR-alpha, was also significantly lower in SIRT1 LKO mice.
Formal Description
Interaction-ID: 5765

gene/protein

SIRT1

affects_expression of

gene/protein

Cyp4A14

in liver; after overnight fasting, if SIRT1 is knocked out in liver
Comment SIRT1 LKO mice displayed reduced expression of several PPAR-alpha target genes after overnight fasting: CPT1a, AOX, CD36, Cyp4A14, CytoC, and PGC-1a. Interestingly, the expression of PPAR-gamma co-activator 1-alpha (PGC-1alpha), a transcription co-factor known to activate PPAR-alpha, was also significantly lower in SIRT1 LKO mice.
Formal Description
Interaction-ID: 5766

gene/protein

SIRT1

affects_expression of

gene/protein

CYCS

in liver; after overnight fasting, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for CYCS
Comment SIRT1 LKO mice displayed reduced expression of several PPAR-alpha target genes after overnight fasting: CPT1a, AOX, CD36, Cyp4A14, CytoC, and PGC-1a. Interestingly, the expression of PPAR-gamma co-activator 1-alpha (PGC-1alpha), a transcription co-factor known to activate PPAR-alpha, was also significantly lower in SIRT1 LKO mice.
Formal Description
Interaction-ID: 5768

gene/protein

SIRT1

affects_expression of

gene/protein

PPARGC1A

in liver; after overnight fasting, if SIRT1 is knocked out in liver
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: 5777

gene/protein

SIRT1

affects_activity of

in liver
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 SIRT1 interacts with PPAR-alpha and is required for the activation of PGC-1alpha.
Formal Description
Interaction-ID: 5788

gene/protein

SIRT1

increases_activity of

gene/protein

PPARGC1A

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 Although SIRT1 LKO mice showed no body weight abnormality on a chow diet, they gained significantly more weight than control mice on the western diet. Consistent with diet-induced obesity, SIRT1 LKO mice showed greater lipid accumulation in the liver compared to control mice. Their serum free fatty acid levels were also significantly increased as compared to control mice. Additionally, serum beta-hydroxybutyrate, a marker for fatty acid oxidation and ketogenesis in the liver, was significantly lower in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 5793

gene/protein

SIRT1

affects_activity of

disease

Obesity

if SIRT1 is knocked out in liver
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: 5796

gene/protein

SIRT1

affects_expression of

gene/protein

CPT1A

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for 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: 5804

gene/protein

SIRT1

affects_expression of

gene/protein

CPT2

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for 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: 5805

gene/protein

SIRT1

affects_expression of

gene/protein

ACAD

in liver; on high-fat diet, if SIRT1 is knocked out in liver
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: 5806

gene/protein

SIRT1

decreases_expression of

gene/protein

ACOX1

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for 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: 5807

gene/protein

SIRT1

affects_expression of

gene/protein

CD36

in liver; on high-fat diet, if SIRT1 is knocked out in liver
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: 5808

gene/protein

SIRT1

affects_expression of

gene/protein

Cyp4A14

in liver; on high-fat diet, if SIRT1 is knocked out in liver
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: 5809

gene/protein

SIRT1

affects_expression of

gene/protein

Cyp4A10

in liver; on high-fat diet, if SIRT1 is knocked out in liver
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: 5811

gene/protein

SIRT1

affects_activity of

in liver; on high-fat diet, if SIRT1 is knocked out in liver
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: 5820

gene/protein

SIRT1

affects_expression of

gene/protein

CYCS

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for 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: 5821

gene/protein

SIRT1

affects_expression of

gene/protein

COX4

in liver; on high-fat diet, if SIRT1 is knocked out in liver
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: 5843

gene/protein

SIRT1

affects_expression of

gene/protein

COX5B

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for COX5B
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 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: 5849

gene/protein

SIRT1

affects_activity of

in liver; on high-fat diet, if SIRT1 is knocked out in liver
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: 5850

gene/protein

SIRT1

affects_expression of

gene/protein

PPARGC1A

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Comment SIRT1 LKO mice on high-fat diet displayed significantly lower mRNA levels of mitochondrial glycerol-3-phosphate acyltransferase (mtGPAT), acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT1), and acyl coenzyme A: diacylglycerol acyltransferase 2 (DGAT2), genes involved in the esterification of fatty acids to glycerol for the synthesis of triglycerides, suggesting that the increase in liver free fatty acids in SIRT1 LKO mice may also be a consequence of impaired fatty acid esterification.
Formal Description
Interaction-ID: 5851

gene/protein

SIRT1

affects_expression of

gene/protein

GPAM

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Comment SIRT1 LKO mice on high-fat diet displayed significantly lower mRNA levels of mitochondrial glycerol-3-phosphate acyltransferase (mtGPAT), acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT1), and acyl coenzyme A: diacylglycerol acyltransferase 2 (DGAT2), genes involved in the esterification of fatty acids to glycerol for the synthesis of triglycerides, suggesting that the increase in liver free fatty acids in SIRT1 LKO mice may also be a consequence of impaired fatty acid esterification.
Formal Description
Interaction-ID: 5852

gene/protein

SIRT1

affects_expression of

gene/protein

DGAT1

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Comment SIRT1 LKO mice on high-fat diet displayed significantly lower mRNA levels of mitochondrial glycerol-3-phosphate acyltransferase (mtGPAT), acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT1), and acyl coenzyme A: diacylglycerol acyltransferase 2 (DGAT2), genes involved in the esterification of fatty acids to glycerol for the synthesis of triglycerides, suggesting that the increase in liver free fatty acids in SIRT1 LKO mice may also be a consequence of impaired fatty acid esterification.
Formal Description
Interaction-ID: 5853

gene/protein

SIRT1

affects_expression of

gene/protein

DGAT2

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Comment SIRT1 LKO mice on high-fat diet displayed significantly lower mRNA levels of mitochondrial glycerol-3-phosphate acyltransferase (mtGPAT), acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT1), and acyl coenzyme A: diacylglycerol acyltransferase 2 (DGAT2), genes involved in the esterification of fatty acids to glycerol for the synthesis of triglycerides, suggesting that the increase in liver free fatty acids in SIRT1 LKO mice may also be a consequence of impaired fatty acid esterification.
Formal Description
Interaction-ID: 5854

gene/protein

SIRT1

affects_activity of

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Comment Cyp7A1, the rate-limiting enzyme involved in the conversion of cholesterol to bile acids, was decreased in SIRT1 LKO mice on high-fat diet, suggesting that the accumulation of hepatic cholesterol may be the result of diminished bile synthesis.
Formal Description
Interaction-ID: 5855

gene/protein

SIRT1

affects_activity of

gene/protein

CYP7A1

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Comment Hepatic deletion of SIRT1 leads to hepatic inflammation and ER stress on the high-fat diet.
Formal Description
Interaction-ID: 5857

gene/protein

SIRT1

affects_activity of

phenotype

liver inflammation

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Comment Hepatic deletion of SIRT1 leads to hepatic inflammation and ER stress on the high-fat diet.
Formal Description
Interaction-ID: 5858

gene/protein

SIRT1

affects_activity of

in liver; on high-fat diet, if SIRT1 is knocked out in liver
Comment ER stress provokes an ER transmembrane protein kinase, pancreatic ER kinase (PERK), to phosphorylate the alpha subunit of the translation initiation factor (eIF2-alpha) thus blocking cellular protein translation. Comparison of levels of phosphorylated eIF2-alpha in liver extracts of control and SIRT1 LKO mice revealed that SIRT1 LKO mice had a 2.2-fold increase in p-eIF2-alpha protein compared to Lox controls.
Formal Description
Interaction-ID: 5862

gene/protein

SIRT1

affects_quantity of

protein modification

EIF2S1-phos

in liver; if SIRT1 is knocked out in liver
Comment Hyper-activation of c-Jun N-terminal kinase (JNK) through phosphorylation is another marker of ER stress. Phosphorylation of JNK (p-JNK) and its downstream target c-Jun (p-c-Jun) were significantly increased by 2.1-fold and 3.2-fold respectively in SIRT1 LKO mice compared to control mice.
Formal Description
Interaction-ID: 5876

gene/protein

SIRT1

affects_quantity of

protein modification

JUN-phos

in liver; if SIRT1 is knocked out in liver
Comment Infiltration of macrophages into tissues is a hallmark of local inflammation. Analysis of mRNA from livers of SIRT1 LKO mice revealed a 70-80% increase in macrophage markers, including macrophage inflammation protein (MIP1a).
Formal Description
Interaction-ID: 5884

gene/protein

SIRT1

affects_quantity of

gene/protein

CCL3

in liver; if SIRT1 is knocked out in liver
Comment Several proinflammatory molecules that are dramatically induced in PPAR-alpha deficient livers, such as vascular cell adhesion molecule (VCAM-1), serum amyloid A-1 (SAA-1), and interferon (IFN)-gamma inducible protein (CXCL10), were significantly higher in livers of SIRT1 LKO mice compared to Lox controls.
Formal Description
Interaction-ID: 5885

gene/protein

SIRT1

affects_quantity of

gene/protein

VCAM1

in liver; if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for VCAM1
Comment Several proinflammatory molecules that are dramatically induced in PPAR-alpha deficient livers, such as vascular cell adhesion molecule (VCAM-1), serum amyloid A-1 (SAA-1), and interferon (IFN)-gamma inducible protein (CXCL10), were significantly higher in livers of SIRT1 LKO mice compared to Lox controls.
Formal Description
Interaction-ID: 5887

gene/protein

SIRT1

affects_quantity of

gene/protein

SAA1

in liver; if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for SAA1
Comment Several proinflammatory molecules that are dramatically induced in PPAR-alpha deficient livers, such as vascular cell adhesion molecule (VCAM-1), serum amyloid A-1 (SAA-1), and interferon (IFN)-gamma inducible protein (CXCL10), were significantly higher in livers of SIRT1 LKO mice compared to Lox controls.
Formal Description
Interaction-ID: 5888

gene/protein

SIRT1

affects_quantity of

gene/protein

CXCL10

in liver; if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for CXCL10
Comment TNF-alpha and IL-1beta, two major proinflammatory cytokines induced by fat accumulation, were also significantly increased in the liver SIRT1 LKO mice.
Formal Description
Interaction-ID: 5889

gene/protein

SIRT1

affects_quantity of

gene/protein

TNF

in liver; if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for TNF
Comment TNF-alpha and IL-1beta, two major proinflammatory cytokines induced by fat accumulation, were also significantly increased in the liver SIRT1 LKO mice.
Formal Description
Interaction-ID: 5890

gene/protein

SIRT1

affects_quantity of

gene/protein

IL1B

in liver; if SIRT1 is knocked out in liver
Drugbank entries Show/Hide entries for IL1B
Comment After feeding with a high-fat diet, Ser473 phosphorylation of Akt, a key molecule in the insulin signaling pathway, was 80% lower in livers of SIRT1 LKO mice.
Formal Description
Interaction-ID: 5891

gene/protein

SIRT1

affects_quantity of

protein modification

AKT1-phosSer473

in liver; on high-fat diet, if SIRT1 is knocked out in liver
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
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: 13195

gene/protein

SIRT1

affects_activity of

in liver; via PPARA
Comment Although SIRT1 LKO mice showed no body weight abnormality on a chow diet, they gained significantly more weight than control mice on the western diet. Consistent with diet-induced obesity, SIRT1 LKO mice showed greater lipid accumulation in the liver compared to control mice. Their serum free fatty acid levels were also significantly increased as compared to control mice. Additionally, serum beta-hydroxybutyrate, a marker for fatty acid oxidation and ketogenesis in the liver, was significantly lower in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 13196

gene/protein

SIRT1

affects_quantity of

drug/chemical compound

Lipid

in liver; if SIRT1 is knocked out in liver
Comment Although SIRT1 LKO mice showed no body weight abnormality on a chow diet, they gained significantly more weight than control mice on the western diet. Consistent with diet-induced obesity, SIRT1 LKO mice showed greater lipid accumulation in the liver compared to control mice. Their serum free fatty acid levels were also significantly increased as compared to control mice. Additionally, serum beta-hydroxybutyrate, a marker for fatty acid oxidation and ketogenesis in the liver, was significantly lower in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 13197

gene/protein

SIRT1

affects_quantity of

drug/chemical compound

Fatty acid

in blood; if SIRT1 is knocked out in liver
Comment Although SIRT1 LKO mice showed no body weight abnormality on a chow diet, they gained significantly more weight than control mice on the western diet. Consistent with diet-induced obesity, SIRT1 LKO mice showed greater lipid accumulation in the liver compared to control mice. Their serum free fatty acid levels were also significantly increased as compared to control mice. Additionally, serum beta-hydroxybutyrate, a marker for fatty acid oxidation and ketogenesis in the liver, was significantly lower in the SIRT1 LKO mice.
Formal Description
Interaction-ID: 13198

gene/protein

SIRT1

affects_quantity of

drug/chemical compound

(R)-3-Hydroxybutanoate

in blood; if SIRT1 is knocked out in liver