General Information:

Id: 386
Diseases: Diabetes mellitus, type II - [OMIM]
Fatty liver disease, nonalcoholic
Insulin resistance
Mus musculus
male
mouse transduced with adenoviruses expressing either murine mtGPAT (GPAM) or a catalytically inactive variant of the enzyme
article
Reference: Linden D et al.(2006) Liver-directed overexpression of mitochondrial glycerol-3-phosphate acyltransferase results in hepatic steatosis, increased triacylglycerol secretion and reduced fatty acid oxidation FASEB J. 20: 434-443 [PMID: 16507761]

Interaction Information:

Comment To study the in vivo effects of hepatic mtGPAT overexpression, mice were transduced with adenoviruses expressing either murine mtGPAT or a catalytically inactive variant of the enzyme. The overexpression was liver specific and decreased between day 4 and 11 after treatment. After 4 days, Ad-mtGPAT-treated mice had 13% heavier livers than Ad-mtGPAT-mut-treated mice.
Formal Description
Interaction-ID: 1615

gene/protein

Mitochondrial GPAT

affects_quantity of

tissue/cell line

liver

if mitochondrial GPAT is overexpressed in liver
Comment Adipocyte differentiation-related protein (ADRP) is expressed in hepatocytes and regarded as a sensitive marker for accumulation of intracellular lipid droplets. mtGPAT but not mtGPAT-mut overexpression resulted in a massive protein expression of ADRP in the liver.
Formal Description
Interaction-ID: 1616

gene/protein

Mitochondrial GPAT

affects_expression of

gene/protein

PLIN2

in liver; if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression did not affect liver content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine, sphingomyelin, lysolecithin, cholesterol, or CE after 4 or 11 days. These results indicate that hepatic mtGPAT overexpression directs fatty acids into DAG and TAG rather than phospholipids or CE in vivo in mice leading to hepatic steatosis.
Formal Description
Interaction-ID: 1618

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

drug/chemical compound

Phosphatidylcholine

in liver; if mitochondrial GPAT is overexpressed in liver
Comment Both palmitic acid (16:0) and stearic acid (18:0) content of DAG and TAG were increased in mtGPAT overexpressing livers. 18:1 was 2.3-fold increased in DAG and both 16:1 and 18:1 were increased in TAG, 21- and 15-fold, respectively. Also 18:2 was increased in TAG.
Formal Description
Interaction-ID: 1710

phenotype

Mitochondrial GPAT

affects_activity of

Comment mRNA expression of stearoyl-CoA desaturase-1 (SCD-1), the major enzyme that catalyses mono-unsaturation of fatty acids in liver, was up-regulated 10-fold in the liver after mtGPAT overexpression.
Formal Description
Interaction-ID: 1711

gene/protein

Mitochondrial GPAT

increases_expression of

gene/protein

SCD

in liver; if mitochondrial GPAT is overexpressed in liver
Comment Although mtGPAT overexpression in vivo did not affect the total amount of phospholipids, the saturation of the first position fatty acid in liver PE increased.
Formal Description
Interaction-ID: 1712

gene/protein

Mitochondrial GPAT

affects_activity of

Comment The expression of sterol regulatory element binding protein-1 (SREBP-1) and peroxisome proliferator-activated receptor (PPAR) gamma-1 and PPARgamma-2 was not influenced by mtGPAT overexpression.
Formal Description
Interaction-ID: 1713

gene/protein

Mitochondrial GPAT

NOT affects_expression of

gene/protein

SREBF1

in liver; if mitochondrial GPAT is overexpressed in liver
Comment In contrast to SCD-1 mRNA, none of the other investigated SREBP-1 downstream target genes: ATP citrate lyase, acetyl-CoA carboxylase (ACC1) mRNA levels or fatty acid synthase (FAS) protein levels were influenced by mtGPAT overexpression.
Formal Description
Interaction-ID: 1714

gene/protein

Mitochondrial GPAT

NOT affects_expression of

gene/protein

ACLY

if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression did not affect liver malonyl-CoA levels.
Formal Description
Interaction-ID: 1715

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

drug/chemical compound

Malonyl-CoA

in liver; if mitochondrial GPAT is overexpressed in liver
Comment The mRNA expression levels of phosphoenolpyruvate carboxykinase and glucokinase, two enzymes involved in gluconeogenesis and glycolysis, respectively, were not transcriptionally regulated after mtGPAT overexpression.
Formal Description
Interaction-ID: 1717

gene/protein

Mitochondrial GPAT

NOT affects_expression of

gene/protein

PCK

if mitochondrial GPAT is overexpressed in liver
Comment Hepatic overexpression of mtGPAT resulted in reduced liver fatty acid oxidation compared with Ad-mtGPAT-mut-treated mice both when related to amount of protein and total liver mass.
Formal Description
Interaction-ID: 1718

gene/protein

Mitochondrial GPAT

decreases_activity of

if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression did not affect mRNA levels of PPAR-alpha or its downstream target genes: acyl-CoA oxidase (ACO), medium-chain acyl-CoA dehydrogenase (MCAD) or CPT-1.
Formal Description
Interaction-ID: 1719

gene/protein

Mitochondrial GPAT

NOT affects_expression of

gene/protein

PPARA

if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for PPARA
Comment mtGPAT overexpression had no effect on plasma glucose or insulin levels, however both plasma TAG and cholesterol levels were increased (27% and 20%, respectively) after 4 days in mice treated with Ad-mtGPAT compared with Ad-mtGPAT-mut, indicating that the VLDL secretion from the liver may be affected by hepatic mtGPAT overexpression.
Formal Description
Interaction-ID: 1720

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

drug/chemical compound

Glucose

in blood; if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression in vivo specifically increased hepatic TAG and DAG levels and decreased the availability of fatty acids for beta-oxidation.
Formal Description
Interaction-ID: 1721

gene/protein

Mitochondrial GPAT

increases_quantity of

drug/chemical compound

Triacylglycerol

in liver; if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression did not affect liver content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine, sphingomyelin, lysolecithin, cholesterol, or CE after 4 or 11 days. These results indicate that hepatic mtGPAT overexpression directs fatty acids into DAG and TAG rather than phospholipids or CE in vivo in mice leading to hepatic steatosis.
Formal Description
Interaction-ID: 12675

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

drug/chemical compound

Phosphatidylethanolamine

in liver; if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for
Comment mtGPAT overexpression did not affect liver content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine, sphingomyelin, lysolecithin, cholesterol, or CE after 4 or 11 days. These results indicate that hepatic mtGPAT overexpression directs fatty acids into DAG and TAG rather than phospholipids or CE in vivo in mice leading to hepatic steatosis.
Formal Description
Interaction-ID: 12676

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

drug/chemical compound

Phosphatidylserine

in liver; if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for
Comment mtGPAT overexpression did not affect liver content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine, sphingomyelin, lysolecithin, cholesterol, or CE after 4 or 11 days. These results indicate that hepatic mtGPAT overexpression directs fatty acids into DAG and TAG rather than phospholipids or CE in vivo in mice leading to hepatic steatosis.
Formal Description
Interaction-ID: 12677

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

drug/chemical compound

Sphingomyelin

in liver; if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression did not affect liver content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine, sphingomyelin, lysolecithin, cholesterol, or CE after 4 or 11 days. These results indicate that hepatic mtGPAT overexpression directs fatty acids into DAG and TAG rather than phospholipids or CE in vivo in mice leading to hepatic steatosis.
Formal Description
Interaction-ID: 12678

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

drug/chemical compound

Lysolecithin

in liver; if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression did not affect liver content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine, sphingomyelin, lysolecithin, cholesterol, or CE after 4 or 11 days. These results indicate that hepatic mtGPAT overexpression directs fatty acids into DAG and TAG rather than phospholipids or CE in vivo in mice leading to hepatic steatosis.
Formal Description
Interaction-ID: 12679

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

drug/chemical compound

Cholesterol

in liver; if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for
Comment mtGPAT overexpression did not affect liver content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine, sphingomyelin, lysolecithin, cholesterol, or CE after 4 or 11 days. These results indicate that hepatic mtGPAT overexpression directs fatty acids into DAG and TAG rather than phospholipids or CE in vivo in mice leading to hepatic steatosis.
Formal Description
Interaction-ID: 12685

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

drug/chemical compound

Cholesterol ester

in liver; if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression did not affect liver content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine, sphingomyelin, lysolecithin, cholesterol, or CE after 4 or 11 days. These results indicate that hepatic mtGPAT overexpression directs fatty acids into DAG and TAG rather than phospholipids or CE in vivo in mice leading to hepatic steatosis.
Formal Description
Interaction-ID: 12686

gene/protein

Mitochondrial GPAT

affects_activity of

disease

Fatty liver disease, nonalcoholic

if mitochondrial GPAT is overexpressed in liver
Comment The expression of sterol regulatory element binding protein-1 (SREBP-1) and peroxisome proliferator-activated receptor (PPAR) gamma-1 and PPARgamma-2 was not influenced by mtGPAT overexpression.
Formal Description
Interaction-ID: 12688

gene/protein

Mitochondrial GPAT

NOT affects_expression of

gene/protein

PPARG

in liver; if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for PPARG
Comment In contrast to SCD-1 mRNA, none of the other investigated SREBP-1 downstream target genes: ATP citrate lyase, acetyl-CoA carboxylase (ACC1) mRNA levels or fatty acid synthase (FAS) protein levels were influenced by mtGPAT overexpression.
Formal Description
Interaction-ID: 12689

gene/protein

Mitochondrial GPAT

NOT affects_expression of

gene/protein

ACACA

if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for ACACA
Comment In contrast to SCD-1 mRNA, none of the other investigated SREBP-1 downstream target genes: ATP citrate lyase, acetyl-CoA carboxylase (ACC1) mRNA levels or fatty acid synthase (FAS) protein levels were influenced by mtGPAT overexpression.
Formal Description
Interaction-ID: 12690

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

gene/protein

FASN

if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for FASN
Comment The mRNA expression levels of phosphoenolpyruvate carboxykinase and glucokinase, two enzymes involved in gluconeogenesis and glycolysis, respectively, were not transcriptionally regulated after mtGPAT overexpression.
Formal Description
Interaction-ID: 12692

gene/protein

Mitochondrial GPAT

NOT affects_expression of

gene/protein

GCK

if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for GCK
Comment mtGPAT overexpression did not affect mRNA levels of PPAR-alpha or its downstream target genes: acyl-CoA oxidase (ACO), medium-chain acyl-CoA dehydrogenase (MCAD) or CPT-1.
Formal Description
Interaction-ID: 12695

gene/protein

Mitochondrial GPAT

NOT affects_expression of

gene/protein

ACOX

if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression did not affect mRNA levels of PPAR-alpha or its downstream target genes: acyl-CoA oxidase (ACO), medium-chain acyl-CoA dehydrogenase (MCAD) or CPT-1.
Formal Description
Interaction-ID: 12697

gene/protein

Mitochondrial GPAT

NOT affects_expression of

gene/protein

ACADM

if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for ACADM
Comment mtGPAT overexpression did not affect mRNA levels of PPAR-alpha or its downstream target genes: acyl-CoA oxidase (ACO), medium-chain acyl-CoA dehydrogenase (MCAD) or CPT-1.
Formal Description
Interaction-ID: 12698

gene/protein

Mitochondrial GPAT

NOT affects_expression of

gene/protein

CPT1A

if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for CPT1A
Comment mtGPAT overexpression had no effect on plasma glucose or insulin levels, however both plasma TAG and cholesterol levels were increased (27% and 20%, respectively) after 4 days in mice treated with Ad-mtGPAT compared with Ad-mtGPAT-mut, indicating that the VLDL secretion from the liver may be affected by hepatic mtGPAT overexpression.
Formal Description
Interaction-ID: 12703

gene/protein

Mitochondrial GPAT

NOT affects_quantity of

complex/PPI

Insulin

in blood; if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression had no effect on plasma glucose or insulin levels, however both plasma TAG and cholesterol levels were increased (27% and 20%, respectively) after 4 days in mice treated with Ad-mtGPAT compared with Ad-mtGPAT-mut, indicating that the VLDL secretion from the liver may be affected by hepatic mtGPAT overexpression.
Formal Description
Interaction-ID: 12704

gene/protein

Mitochondrial GPAT

affects_quantity of

drug/chemical compound

Triacylglycerol

in blood; if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression had no effect on plasma glucose or insulin levels, however both plasma TAG and cholesterol levels were increased (27% and 20%, respectively) after 4 days in mice treated with Ad-mtGPAT compared with Ad-mtGPAT-mut, indicating that the VLDL secretion from the liver may be affected by hepatic mtGPAT overexpression.
Formal Description
Interaction-ID: 12705

gene/protein

Mitochondrial GPAT

affects_quantity of

drug/chemical compound

Cholesterol

in blood; if mitochondrial GPAT is overexpressed in liver
Drugbank entries Show/Hide entries for
Comment mtGPAT overexpression in vivo specifically increased hepatic TAG and DAG levels and decreased the availability of fatty acids for beta-oxidation.
Formal Description
Interaction-ID: 12706

gene/protein

Mitochondrial GPAT

increases_quantity of

drug/chemical compound

Diacylglycerol

in liver; if mitochondrial GPAT is overexpressed in liver
Comment mtGPAT overexpression in vivo specifically increased hepatic TAG and DAG levels and decreased the availability of fatty acids for beta-oxidation.
Formal Description
Interaction-ID: 12707

gene/protein

Mitochondrial GPAT

decreases_activity of

in liver; if mitochondrial GPAT is overexpressed in liver