)| PMID |
18846047 ( ) |
|---|---|
| Title | Obesity upregulates genes involved in oxidative phosphorylation in livers of diabetic patients. |
| Abstract | Obesity is a major cause of insulin resistance and contributes to the development of type 2 diabetes. The altered expression of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) has been regarded as a key change in insulin-sensitive organs of patients with type 2 diabetes. This study explores possible molecular signatures of obesity and examines the clinical significance of OXPHOS gene expression in the livers of patients with type 2 diabetes. We analyzed gene expression in the livers of 21 patients with type 2 diabetes (10 obese and 11 nonobese patients; age, 53.0 +/- 2.1 years; BMI, 24.4 +/- 0.9 kg/m(2); fasting plasma glucose, 143.0 +/- 10.6 mg/dl) using a DNA chip. We screened 535 human pathways and extracted those metabolic pathways significantly altered by obesity. Genes involved in the OXPHOS pathway, together with glucose and lipid metabolism pathways, were coordinately upregulated in the liver in association with obesity. The mean centroid of OXPHOS gene expression was significantly correlated with insulin resistance indices and the hepatic expression of genes involved in gluconeogenesis, reactive oxygen species (ROS) generation, and transcriptional factors and nuclear co-activators associated with energy homeostasis. In conclusion, obesity may affect the pathophysiology of type 2 diabetes by upregulating genes involved in OXPHOS in association with insulin resistance markers and the expression of genes involved in hepatic gluconeogenesis and ROS generation. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 6081 | INS | insulin | 35 | insulin | |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | 15 | pgc 1 alpha | PGC-1 | pgc 1 alpha | |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | 7 | PPAR-alpha | PPARs | |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | 6 | ppar gamma | PPAR-gamma | |
| 30022 | PPARGC1B | peroxisome proliferator-activated receptor gamma, coactivator 1 beta | 6 | pgc 1 beta | pgc 1 beta | |
| 8725 | PCK2 | phosphoenolpyruvate carboxykinase 2 (mitochondrial) | 5 | PEPCK2 | PEPCK | |
| 13633 | ADIPOQ | adiponectin, C1Q and collagen domain containing | 4 | adiponectin | |
| 4552 | GPT | glutamic-pyruvate transaminase (alanine aminotransferase) | 4 | alanine aminotransferase | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 4 | nadph oxidase | |
| 12518 | UCP2 | uncoupling protein 2 (mitochondrial, proton carrier) | 3 | uncoupling protein 2 | UCP2 | UCP-2 | |
| 6553 | LEP | leptin | 2 | leptin | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 2 | tumor necrosis factor alpha | |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | 2 | NF-kappaB | |
| 1516 | CAT | catalase | 2 | catalase | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 1 | NCF2 | |
| 2642 | CYP4A11 | cytochrome P450, family 4, subfamily A, polypeptide 11 | 1 | CYP4A11 | |
| 2367 | CRP | C-reactive protein, pentraxin-related | 1 | c reactive protein | |
| 2328 | CPT1A | carnitine palmitoyltransferase 1A (liver) | 1 | carnitine palmitoyltransferase | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 1 | CYBB | |
| 4458 | GPI | glucose phosphate isomerase | 1 | glucose phosphate isomerase | |
| 8951 | SERPINE2 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 | 1 | plasminogen activator inhibitor type 1 | |
| 25806 | GSTCD | glutathione S-transferase, C-terminal domain containing | 1 | glutathione s transferase | |
| 8636 | PC | pyruvate carboxylase | 1 | pyruvate carboxylase | |
| 8548 | P4HB | procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), beta polypeptide | 1 | protein disulfide isomerase | |
| 7996 | NRF1 | nuclear respiratory factor 1 | 1 | nuclear respiratory factor 1 | |
| 82 | ACAA1 | acetyl-Coenzyme A acyltransferase 1 (peroxisomal 3-oxoacyl-Coenzyme A thiolase) | 1 | acetyl coenzyme a acyltransferase | |
| 121 | ACOX3 | acyl-Coenzyme A oxidase 3, pristanoyl | 1 | ACOX3 | |
| 4061 | SLC37A4 | solute carrier family 37 (glucose-6-phosphate transporter), member 4 | 1 | glucose 6 phosphatase | |
| 2631 | CYP2E1 | cytochrome P450, family 2, subfamily E, polypeptide 1 | 1 | CYP2E1 | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 1 | NCF1 | |
| 336 | AGTR1 | angiotensin II receptor, type 1 | 1 | angiotensin ii receptor | |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | 1 | angiotensin converting enzyme | |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | 1 | cytochrome c oxidase | |
| 7889 | NOX1 | NADPH oxidase 1 | 1 | NOX1 | |
| 9235 | PPARD | peroxisome proliferator-activated receptor delta | 1 | ppar beta | |
| 1663 | CD36 | CD36 molecule (thrombospondin receptor) | 1 | CD36 | |
| 8724 | PCK1 | phosphoenolpyruvate carboxykinase 1 (soluble) | 1 | PEPCK1 | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 1 | CYBA | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 13633 | ADIPOQ | adiponectin, C1Q and collagen domain containing | adiponectin | 1.5 | free fatty acids or adipocytokines such as tumor necrosis factor-alpha adiponectin and leptin between the overweight and normal-weight groups ( Supplementary |
| 8725 | PCK2 | phosphoenolpyruvate carboxykinase 2 (mitochondrial) | PEPCK | 1.4 | encoding the key gluconeogenesis enzymes such as phosphoenolpyruvate carboxykinase (PEPCK), PEPCK phosphoglycerate kinase fructose-1 6-bisphosphatase glucose phosphate isomerase and glucose-6-phosphatase (G-6-Pase) |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 0.9 | We focused on the peroxisome proliferator_amp_#8211 activated receptor PPAR -alpha and PPAR-gamma as master control genes for the beta-oxidation |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-gamma | 1.3 | focused on the peroxisome proliferator_amp_#8211 activated receptor PPAR -alpha and PPAR-gamma as master control genes for the beta-oxidation of fatty acids |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR-alpha | 0.3 | The PPAR-alpha and PPAR-gamma genes were both upregulated in obesity (obese/nonobese: obese |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-gamma | 1.3 | The PPAR-alpha and PPAR-gamma genes were both upregulated in obesity (obese/nonobese: obese nonobese 1.50 |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-gamma | 1.3 | The PPAR-gamma gene expression level correlated with BMI ( r = 0.611 |
| 1663 | CD36 | CD36 molecule (thrombospondin receptor) | CD36 | 1.1 | well as the expression levels of its target genes the CD36 gene ( 27 ( r = 0.864 P _lt_ 0.001 |
| 12518 | UCP2 | uncoupling protein 2 (mitochondrial, proton carrier) | UCP2 | 1.9 | = 0.864 P _lt_ 0.001 and uncoupling protein 2 ( UCP2 gene ( 28 29 ( r = 0.532 P = |
| 8725 | PCK2 | phosphoenolpyruvate carboxykinase 2 (mitochondrial) | PEPCK | 1.4 | In addition gluconeogenic enzymes such as PEPCK require ATP for their catalytic actions |
| 8724 | PCK1 | phosphoenolpyruvate carboxykinase 1 (soluble) | PEPCK1 | 1.2 | significantly correlated with the expression of gluconeogenic genes such as PEPCK1 PEPCK2 and glucose transporter type 2 ( Table 3 |
| 8725 | PCK2 | phosphoenolpyruvate carboxykinase 2 (mitochondrial) | PEPCK2 | 1.4 | correlated with the expression of gluconeogenic genes such as PEPCK1 PEPCK2 and glucose transporter type 2 ( Table 3 |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | PGC-1 | 1.1 | reported to be associated with OXPHOS or energy homeostasis including PGC-1 alpha PGC-1 beta nuclear res piratory factor-1 PPARs estrogen-related receptors |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | PGC-1 | 1.1 | be associated with OXPHOS or energy homeostasis including PGC-1 alpha PGC-1 beta nuclear res piratory factor-1 PPARs estrogen-related receptors thyroid receptors |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARs | 0.3 | homeostasis including PGC-1 alpha PGC-1 beta nuclear res piratory factor-1 PPARs estrogen-related receptors thyroid receptors steroid receptor co-activator-1 and transcriptional intermediary |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | PGC-1 | 1.1 | Gene expression for PGC-1 beta PPAR-alpha steroid receptor co-activator-1 TR-alpha and transcriptional intermediary factor-2 |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR-alpha | 0.3 | Gene expression for PGC-1 beta PPAR-alpha steroid receptor co-activator-1 TR-alpha and transcriptional intermediary factor-2 was significantly |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | PGC-1 | 1.1 | However the expression of PGC-1 alpha which has been reported to be correlated with OXPHOS |
| 121 | ACOX3 | acyl-Coenzyme A oxidase 3, pristanoyl | ACOX3 | 0.3 | encoding enzymes associated with peroxisomal beta-oxidation of fatty acids ( ACOX3 the nicotinamide adenine dinucleotide phosphate (NADPH) NADPH oxidase complex ( |
| 7889 | NOX1 | NADPH oxidase 1 | NOX1 | 0.9 | the nicotinamide adenine dinucleotide phosphate (NADPH) NADPH oxidase complex ( NOX1 CYBB CYBA NCF1 and NCF2 and the stress-responsive cytochromes ( |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | CYBB | 0.3 | nicotinamide adenine dinucleotide phosphate (NADPH) NADPH oxidase complex ( NOX1 CYBB CYBA NCF1 and NCF2 and the stress-responsive cytochromes ( CYP2E1 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | CYBA | 0.3 | adenine dinucleotide phosphate (NADPH) NADPH oxidase complex ( NOX1 CYBB CYBA NCF1 and NCF2 and the stress-responsive cytochromes ( CYP2E1 and |
| 2631 | CYP2E1 | cytochrome P450, family 2, subfamily E, polypeptide 1 | CYP2E1 | 0.3 | CYBB CYBA NCF1 and NCF2 and the stress-responsive cytochromes ( CYP2E1 and CYP4A11 all of which are involved in ROS generation |
| 2642 | CYP4A11 | cytochrome P450, family 4, subfamily A, polypeptide 11 | CYP4A11 | 0.3 | NCF1 and NCF2 and the stress-responsive cytochromes ( CYP2E1 and CYP4A11 all of which are involved in ROS generation in the |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | NCF1 | 0.1 | dinucleotide phosphate (NADPH) NADPH oxidase complex ( NOX1 CYBB CYBA NCF1 and NCF2 and the stress-responsive cytochromes ( CYP2E1 and CYP4A11 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | NCF2 | 0.1 | dinucleotide phosphate (NADPH) NADPH oxidase complex ( NOX1 CYBB CYBA NCF1 and NCF2 and the stress-responsive cytochromes ( CYP2E1 and CYP4A11 |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | PGC-1 | 1.1 | skeletal muscle of patients with type 2 diabetes in which PGC-1 alpha-responsive genes of the OXPHOS pathway are coordinately downregulated and |
| 8725 | PCK2 | phosphoenolpyruvate carboxykinase 2 (mitochondrial) | PEPCK | 1.4 | upregulation of genes that encode the enzymes of gluconeogenesis including PEPCK and G-6-Pase with increases in insulin resistance |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR-alpha | 0.3 | pathway was supported by the upregulation of the genes for PPAR-alpha and PPAR-beta-oxidation ( 25 26 |
| 12518 | UCP2 | uncoupling protein 2 (mitochondrial, proton carrier) | UCP-2 | 1.6 | The expression level of UCP-2 a target gene of PPAR- 28 29 was significantly correlated |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR- | 0.8 | The expression level of UCP-2 a target gene of PPAR- 28 29 was significantly correlated with that of the PPAR-gene. |
| 13633 | ADIPOQ | adiponectin, C1Q and collagen domain containing | adiponectin | 1.5 | factors alone because the serum levels of adipocytokines such as adiponectin leptin and tumor necrosis factor-alpha did not change significantly in |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.3 | in ROS generation in bovine aortic endothelial cells thereby preventing NF-kappaB activation ( 42 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.3 | OXPHOS pathway may stimulate ROS formation in the liver activate NF-kappaB and increase inflammation-associated insulin resistance ( 1 |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | PGC-1 | 1.1 | type 2 diabetes ( 9 10 the expression level of PGC-1 alpha was not significantly correlated with the severity of either |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | PGC-1 | 1.1 | associated with the OXPHOS pathway or energy homeostasis such as PGC-1 beta nuclear respiratory factor-1 PPARs estrogen-related receptors and thyroid receptors |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARs | 0.3 | or energy homeostasis such as PGC-1 beta nuclear respiratory factor-1 PPARs estrogen-related receptors and thyroid receptors ( 8 were significantly correlated |
| 8725 | PCK2 | phosphoenolpyruvate carboxykinase 2 (mitochondrial) | PEPCK | 1.4 | NADPH nicotinamide adenine dinucleotide phosphate PEPCK phosphoenolpyruvate carboxykinase TCA tricarboxylic acid |
| 6081 | INS | insulin | insulin | 1.0 | the identification of the upstream master gene s controlling the expression of the oxphos pathway genes is an important issue in elucidating the mechanism s underlying obesity induced insulin resistance. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | along with the oxphos pathway genes the genes encoding enzymes associated with ros generation such as those involved in the mitochondrial and peroxisomal beta oxidation of fatty acids 15 nadph oxidase 30 and stress responsive cytochromes 31 were also upregulated in obesity. |
| 1516 | CAT | catalase | catalase | 1.0 | accordingly genes encoding redox and ros scavenging systems such as catalase and glutathione peroxidase may be upregulated in obesity. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these findings suggest that obesity causes oxidative stress in the liver partly attributable to ros generated from the oxphos pathway together with the peroxisomal beta oxidation of fatty acids nadph oxidase and cytochromes. |
| 6081 | INS | insulin | insulin | 1.0 | in summary we provide the first evidence that the increased expression of genes involved in oxphos in the human liver links obesity in diabetes with insulin resistance. |
| 7996 | NRF1 | nuclear respiratory factor 1 | nuclear respiratory factor 1 | 1.0 | instead transcriptional factors or nuclear co activators reportedly associated with the oxphos pathway or energy homeostasis such as pgc 1 beta nuclear respiratory factor 1 ppars estrogen related receptors and thyroid receptors 8 were significantly correlated with the mean centroid of the oxphos pathway genes. |
| 30022 | PPARGC1B | peroxisome proliferator-activated receptor gamma, coactivator 1 beta | pgc 1 beta | 1.0 | instead transcriptional factors or nuclear co activators reportedly associated with the oxphos pathway or energy homeostasis such as pgc 1 beta nuclear respiratory factor 1 ppars estrogen related receptors and thyroid receptors 8 were significantly correlated with the mean centroid of the oxphos pathway genes. |
| 30022 | PPARGC1B | peroxisome proliferator-activated receptor gamma, coactivator 1 beta | pgc 1 beta | 1.0 | instead transcriptional factors or nuclear co activators reportedly associated with the oxphos pathway or energy homeostasis such as pgc 1 beta nuclear respiratory factor 1 ppars estrogen related receptors and thyroid receptors 8 were significantly correlated with the mean centroid of the oxphos pathway genes. |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | pgc 1 alpha | 1.0 | note that unlike in the skeletal muscle of patients with type 2 diabetes 9 10 the expression level of pgc 1 alpha was not significantly correlated with the severity of either obesity or insulin resistance or with the expression levels of genes encoding the enzymes of gluconeogenesis data not shown or the oxphos p |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | pgc 1 alpha | 1.0 | note that unlike in the skeletal muscle of patients with type 2 diabetes 9 10 the expression level of pgc 1 alpha was not significantly correlated with the severity of either obesity or insulin resistance or with the expression levels of genes encoding the enzymes of gluconeogenesis data not shown or the oxphos |
| 6081 | INS | insulin | insulin | 1.0 | indeed the expression of oxphos genes was significantly correlated with the expression of gluconeogenic genes and with insulin resistance suggesting that obesity latently enhances the oxphos pathway and insulin resistance in patients with type 2 diabetes. |
| 6081 | INS | insulin | insulin | 1.0 | resistance suggesting that obesity latently enhances the oxphos pathway and insulin resistance in patients with type 2 diabetes. |
| 6081 | INS | insulin | insulin | 1.0 | note that unlike in the skeletal muscle of patients with type 2 diabetes 9 10 the expression level of pgc 1 alpha was not significantly correlated with the severity of either obesity or insulin resistance or with the expression levels of genes encoding the enzymes of gluconeogenesis data not shown or the oxphos pathway table 3 . |
| 6553 | LEP | leptin | leptin | 1.0 | furthermore hepatic gene expression in obesity did not seem to be altered by adipocyte derived factors alone because the serum levels of adipocytokines such as adiponectin leptin and tumor necrosis factor alpha did not change significantly in the obese patients |
| 9235 | PPARD | peroxisome proliferator-activated receptor delta | ppar beta | 1.0 | obesity associated upregulation of the fatty acid beta oxidation pathway was supported by the upregulation of the genes for ppar alpha and ppar beta oxidation 25 26 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the pentose phosphate cycle supplies nadph and h + required for fatty acid and cholesterol synthesis and can also lead to ros generation via nadph oxidase 36 . |
| 8636 | PC | pyruvate carboxylase | pyruvate carboxylase | 1.0 | increased fatty acid oxidation promotes the gluconeogenesis pathway in part by maintaining pyruvate carboxylase in an active state 33 . |
| 6081 | INS | insulin | insulin | 1.0 | our comprehensive search for metabolic pathways altered in obesity we found coordinated upregulation of genes that encode the enzymes of gluconeogenesis including pepck and g 6 pase with increases in insulin resistance. |
| 6081 | INS | insulin | insulin | 1.0 | this finding suggests that the moderate deficiency in oxphos that is observed in the skeletal muscle of insulin resistant humans is not a causative factor in diabetes but may instead be a compensatory response 19 20 . |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | pgc 1 alpha | 1.0 | in fact the expression profile in the liver looks like a mirror image of that in the skeletal muscle of patients with type 2 diabetes in which pgc 1 alpha responsive genes of the oxphos pathway are coordinately downregulated and predict total body aerobic capacity 9 10 . |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | pgc 1 alpha | 1.0 | in fact the expression profile in the liver looks like a mirror image of that in the skeletal muscle of patients with type 2 diabetes in which pgc 1 alpha responsive genes of the oxphos pathway are coordinately downregulated and predict total body aerobic capacity 9 10 . |
| 6081 | INS | insulin | insulin | 1.0 | however the causative or compensatory nature of this oxphos gene expression in the pathogenesis of insulin resistance remains controversial 19 . |
| 6081 | INS | insulin | insulin | 1.0 | here we demonstrated that obesity further upregulated type 2 diabetes associated oxphos pathway gene expression with insulin resistance. |
| 1516 | CAT | catalase | catalase | 1.0 | in addition genes encoding ros scavenging systems such as glutathione s transferase protein disulfide isomerase catalase selenoproteins and glutathione peroxidase were upregulated in obesity. |
| 25806 | GSTCD | glutathione S-transferase, C-terminal domain containing | glutathione s transferase | 1.0 | in addition genes encoding ros scavenging systems such as glutathione s transferase protein disulfide isomerase catalase selenoproteins and glutathione peroxidase were upregulated in obesity. |
| 8548 | P4HB | procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), beta polypeptide | protein disulfide isomerase | 1.0 | in addition genes encoding ros scavenging systems such as glutathione s transferase protein disulfide isomerase catalase selenoproteins and glutathione peroxidase were upregulated in obesity. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | genes encoding enzymes associated with peroxisomal beta oxidation of fatty acids acox3 the nicotinamide adenine dinucleotide phosphate nadph oxidase complex nox1 cybb cyba ncf1 and ncf2 and the stress responsive cytochromes cyp2e1 and cyp4a11 all of which are involved in ros generation in the liver 15 30 31 were upregulated in obesity table 4 sup |
| 6081 | INS | insulin | insulin | 1.0 | ssion of genes involved in ros generation increased mitochondrial oxygen flux through the oxphos pathway leads to increased formation of ros as by products 15 and may contribute to the development of insulin resistance in patients with obesity. |
| 30022 | PPARGC1B | peroxisome proliferator-activated receptor gamma, coactivator 1 beta | pgc 1 beta | 1.0 | phos pathway genes in the human liver we analyzed the expression of transcriptional factors and nuclear co activators reported to be associated with oxphos or energy homeostasis including pgc 1 alpha pgc 1 beta nuclear res piratory factor 1 ppars estrogen related receptors thyroid receptors steroid receptor co activator 1 and transcriptional intermediary factor 2 ref 8 . |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | pgc 1 alpha | 1.0 | ession of oxphos pathway genes in the human liver we analyzed the expression of transcriptional factors and nuclear co activators reported to be associated with oxphos or energy homeostasis including pgc 1 alpha pgc 1 beta nuclear res piratory factor 1 ppars estrogen related receptors thyroid receptors steroid receptor co activator 1 and transcriptional intermediary factor 2 ref 8 . |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | pgc 1 alpha | 1.0 | ession of oxphos pathway genes in the human liver we analyzed the expression of transcriptional factors and nuclear co activators reported to be associated with oxphos or energy homeostasis including pgc 1 alpha pgc 1 beta nuclear res piratory factor 1 ppars estrogen related receptors thyroid receptors steroid receptor co activator 1 and transcriptional intermediary factor 2 ref 8 . |
| 6081 | INS | insulin | insulin | 1.0 | furthermore the insulin resistance index quicki was significantly correlated with the expression of gluconeogenic genes data not shown . |
| 6081 | INS | insulin | insulin | 1.0 | hepatic insulin resistance contributes to impaired suppression of gluconeogenesis in humans 3 4 and in various animal models 5 . |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | pgc 1 alpha | 1.0 | however the expression of pgc 1 alpha which has been reported to be correlated with oxphos gene expression in skeletal muscle in type 2 diabetes 9 10 was not correlated with the mean centroid of the oxphos genes in the liver table 3 . |
| 6081 | INS | insulin | insulin | 1.0 | therefore the upregulation of oxphos pathway genes may be associated with insulin resistance and related pathologies such as obesity fatty liver and atherosclerosis. |
| 6081 | INS | insulin | insulin | 1.0 | therefore obesity induced activation of the oxphos pathway may stimulate ros formation in the liver activate nf kappab and increase inflammation associated insulin resistance 1 . |
| 6081 | INS | insulin | insulin | 1.0 | moreover ros have been suggested to play a causal role in experimental models of insulin resistance in hepatocytes and adipocytes 13 41 . |
| 13633 | ADIPOQ | adiponectin, C1Q and collagen domain containing | adiponectin | 1.0 | furthermore hepatic gene expression in obesity did not seem to be altered by adipocyte derived factors alone because the serum levels of adipocytokines such as adiponectin leptin and tumor necrosis factor alpha did not change significantly in the obese patients |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor alpha | 1.0 | furthermore hepatic gene expression in obesity did not seem to be altered by adipocyte derived factors alone because the serum levels of adipocytokines such as adiponectin leptin and tumor necrosis factor alpha did not change significantly in the obese patients |
| 9237 | PPARGC1A | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha | pgc 1 alpha | 1.0 | however the expression of pgc 1 alpha which has been reported to be correlated with oxphos gene expression in skeletal muscle in type 2 diabetes 9 10 was not correlated with the mean centroid of the oxphos genes in the liver table 3 . |
| 30022 | PPARGC1B | peroxisome proliferator-activated receptor gamma, coactivator 1 beta | pgc 1 beta | 1.0 | gene expression for pgc 1 beta ppar alpha steroid receptor co activator 1 tr alpha and transcriptional intermediary factor 2 was significantly correlated with the mean centroid of the oxphos genes table 3 . |
| 30022 | PPARGC1B | peroxisome proliferator-activated receptor gamma, coactivator 1 beta | pgc 1 beta | 1.0 | gene expression for pgc 1 beta ppar alpha steroid receptor co activator 1 tr alpha and transcriptional intermediary factor 2 was significantly correlated with the mean centroid of the oxphos genes table 3 . |
| 30022 | PPARGC1B | peroxisome proliferator-activated receptor gamma, coactivator 1 beta | pgc 1 beta | 1.0 | phos pathway genes in the human liver we analyzed the expression of transcriptional factors and nuclear co activators reported to be associated with oxphos or energy homeostasis including pgc 1 alpha pgc 1 beta nuclear res piratory factor 1 ppars estrogen related receptors thyroid receptors steroid receptor co activator 1 and transcriptional intermediary factor 2 ref 8 . |
| 8951 | SERPINE2 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 | plasminogen activator inhibitor type 1 | 1.0 | with insulin resistance indices such as the fasting serum insulin level homeostasis model assessment of insulin resistance and quicki and tended to be correlated with bmi alanine aminotransferase and plasminogen activator inhibitor type 1 table 2 . |
| 6081 | INS | insulin | insulin | 1.0 | the mean centroid of the oxphos genes in the liver was significantly correlated with insulin resistance indices such as the fasting serum insulin level homeostasis model assessment of insulin resistance and quicki and tended to be correlated with bmi alanine aminotransferase and plasminogen activator inhibitor type 1 table 2 . |
| 4552 | GPT | glutamic-pyruvate transaminase (alanine aminotransferase) | alanine aminotransferase | 1.0 | was significantly correlated with insulin resistance indices such as the fasting serum insulin level homeostasis model assessment of insulin resistance and quicki and tended to be correlated with bmi alanine aminotransferase and plasminogen activator inhibitor type 1 table 2 . |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | cytochrome c oxidase | 1.0 | f nicotinamide adenine dinucleotide nadh _amp_#8211;ubiquinone oxidoreductase complex i succinate_amp_#8211;ubiquinone oxidoreductase complex ii ubiquinol_amp_#8211;cytochrome c reductase complex iii cytochrome c oxidase complex iv and atp synthase complex v . |
| 6081 | INS | insulin | insulin | 1.0 | upregulation of the oxphos pathway and its association with insulin resistance the most significant pathway enzyme genes coordinately altered in obesity were the 144 genes involved in the mitochondrial oxphos pathway permutation p _lt_ 0.00001; table 1 . |
| 12518 | UCP2 | uncoupling protein 2 (mitochondrial, proton carrier) | uncoupling protein 2 | 1.0 | 80 p = 0.001 and quantitative insulin sensitivity check index quicki r = _amp_#8211;0.805 p _lt_ 0.001 as well as the expression levels of its target genes the cd36 gene 27 r = 0.864 p _lt_ 0.001 and uncoupling protein 2 ucp2 gene 28 29 r = 0.532 p = 0.013 . |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | the ppar gamma gene expression level correlated with bmi r = 0.611 p = 0.003 homeostasis model assessment of insulin resistance r = 0.680 p = 0.001 and quantitative insulin sensitivity check index quicki r = _amp_# |
| 6081 | INS | insulin | insulin | 1.0 | the ppar gamma gene expression level correlated with bmi r = 0.611 p = 0.003 homeostasis model assessment of insulin resistance r = 0.680 p = 0.001 and quantitative insulin sensitivity check index quicki r = _amp_#8211;0.805 p _lt_ 0.001 as well as the expression levels of its target genes the cd36 gene 27 r = 0.864 p _lt_ 0.001 and uncoupling protein 2 ucp2 gene 28 29 |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | the ppar alpha and ppar gamma genes were both upregulated in obesity obese/nonobese: 1.50 and 2.00; p = 0.0037 and 0.0546 respectively . |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | we focused on the peroxisome proliferator_amp_#8211;activated receptor ppar alpha and ppar gamma as master control genes for the beta oxidation of fatty acids 25 26 . |
| 2328 | CPT1A | carnitine palmitoyltransferase 1A (liver) | carnitine palmitoyltransferase | 1.0 | genes encoding enzymes of the fatty acid beta oxidation pathway including carnitine palmitoyltransferase and acetyl coenzyme a acyltransferase were upregulated in obesity supplementary figure s1c online . |
| 82 | ACAA1 | acetyl-Coenzyme A acyltransferase 1 (peroxisomal 3-oxoacyl-Coenzyme A thiolase) | acetyl coenzyme a acyltransferase | 1.0 | genes encoding enzymes of the fatty acid beta oxidation pathway including carnitine palmitoyltransferase and acetyl coenzyme a acyltransferase were upregulated in obesity supplementary figure s1c online . |
| 6081 | INS | insulin | insulin | 1.0 | therefore the expression of genes involved in glucose metabolism was coordinately upregulated with insulin resistance in the livers of obese patients with type 2 diabetes. |
| 4458 | GPI | glucose phosphate isomerase | glucose phosphate isomerase | 1.0 | sity was associated with significant upregulation of genes encoding the key gluconeogenesis enzymes such as phosphoenolpyruvate carboxykinase pepck phosphoglycerate kinase fructose 1 6 bisphosphatase glucose phosphate isomerase and glucose 6 phosphatase g 6 pase obese/nonobese: 1.50 1.50 1.38 and 1.57; p = 0.016 0.005 0.016 and 0.042 respectively; figure 1 . |
| 4061 | SLC37A4 | solute carrier family 37 (glucose-6-phosphate transporter), member 4 | glucose 6 phosphatase | 1.0 | cant upregulation of genes encoding the key gluconeogenesis enzymes such as phosphoenolpyruvate carboxykinase pepck phosphoglycerate kinase fructose 1 6 bisphosphatase glucose phosphate isomerase and glucose 6 phosphatase g 6 pase obese/nonobese: 1.50 1.50 1.38 and 1.57; p = 0.016 0.005 0.016 and 0.042 respectively; figure 1 . |
| 13633 | ADIPOQ | adiponectin, C1Q and collagen domain containing | adiponectin | 1.0 | no significant differences were observed in the serum levels of high sensitivity c reactive protein free fatty acids or adipocytokines such as tumor necrosis factor alpha adiponectin and leptin between the overweight and normal weight groups supplementary table s1 online . |
| 2367 | CRP | C-reactive protein, pentraxin-related | c reactive protein | 1.0 | no significant differences were observed in the serum levels of high sensitivity c reactive protein free fatty acids or adipocytokines such as tumor necrosis factor alpha adiponectin and leptin between the overweight and normal weight groups supplementary table s1 online . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor alpha | 1.0 | no significant differences were observed in the serum levels of high sensitivity c reactive protein free fatty acids or adipocytokines such as tumor necrosis factor alpha adiponectin and leptin between the overweight and normal weight groups supplementary table s1 online . |
| 6553 | LEP | leptin | leptin | 1.0 | no significant differences were observed in the serum levels of high sensitivity c reactive protein free fatty acids or adipocytokines such as tumor necrosis factor alpha adiponectin and leptin between the overweight and normal weight groups supplementary table s1 online . |
| 4552 | GPT | glutamic-pyruvate transaminase (alanine aminotransferase) | alanine aminotransferase | 1.0 | bmi was significantly correlated with quicki r = _amp_#8211;0.482 p = 0.037 alanine aminotransferase r = 0.584 p = 0.005 aspartate aminotransferase r = 0.671 p = 0.001 and liver steatosis scores r = 0.598 p = 0.004 . |
| 6081 | INS | insulin | insulin | 1.0 | in addition insulin resistance estimated with homeostasis model assessment of insulin resistance and quicki was also higher in the overweight group and liver steatosis tended to be more severe. |
| 6081 | INS | insulin | insulin | 1.0 | the insulin regimen for all insulin treated patients 2 of 10 obese patients and 5 of 11 nonobese patients was prandial dosing with rapid acting insulin analogue. |
| 4552 | GPT | glutamic-pyruvate transaminase (alanine aminotransferase) | alanine aminotransferase | 1.0 | cimens were obtained from 21 patients with type 2 diabetes 15 men 6 women; mean age 53.0 2.1 years; mean bmi 24.4 0.9 kg/m 2 ; mean fasting plasma glucose 7.94 0.59 mmol/l; mean hba 1c 7.3 0.3%; mean alanine aminotransferase 34.4 5.5 iu/l admitted to kanazawa university hospital between 2000 and 2003. |
| 6081 | INS | insulin | insulin | 1.0 | we further investigated the relationship of insulin resistance indices and hepatic gene expression for glucose and lipid metabolism and ros generation with oxphos gene expression. |
| 6081 | INS | insulin | insulin | 1.0 | in addition whether upregulation or downregulation of oxphos genes contributes to insulin resistance remains controversial 19 20 . |
| 6081 | INS | insulin | insulin | 1.0 | obesity is a major cause of insulin resistance and contributes to the development of type 2 diabetes. |
| 6081 | INS | insulin | insulin | 1.0 | the altered expression of genes involved in mitochondrial oxidative phosphorylation oxphos has been regarded as a key change in insulin sensitive organs of patients with type 2 diabetes. |
| 6081 | INS | insulin | insulin | 1.0 | the mean centroid of oxphos gene expression was significantly correlated with insulin resistance indices and the hepatic expression of genes involved in gluconeogenesis reactive oxygen species ros generation and transcriptional factors and nuclear co activators associated with energy |
| 6081 | INS | insulin | insulin | 1.0 | in conclusion obesity may affect the pathophysiology of type 2 diabetes by upregulating genes involved in oxphos in association with insulin resistance markers and the expression of genes involved in hepatic gluconeogenesis and ros generation. |
| 6081 | INS | insulin | insulin | 1.0 | obesity is a major cause of insulin resistance 1 and contributes to the development of type 2 diabetes. |
| 6081 | INS | insulin | insulin | 1.0 | in patients with diabetes the coexistence of obesity further increases insulin resistance and makes glycemic control difficult 2 . |
| 6081 | INS | insulin | insulin | 1.0 | absolute or relative failure of insulin action on the liver causes impaired suppression of glucose production 3 and hepatic insulin resistance leads to impaired suppression of gluconeogenesis contributing to fasting hyperglycemia in humans 3 4 and in various animal models 5 . |
| 6081 | INS | insulin | insulin | 1.0 | however little is known about how obesity causes hepatic insulin resistance in patients with type 2 diabetes. |
| 6081 | INS | insulin | insulin | 1.0 | recent gene chip technology data suggest that the altered expression of genes involved in mitochondrial oxidative phosphorylation oxphos is a key change in the insulin sensitive organs of patients with type 2 diabetes 8 9 10 11 . |
| 6081 | INS | insulin | insulin | 1.0 | mitochondrial oxphos is a major source of reactive oxygen species ros production in most cells 12 and ros comprise one of the many factors that have been suggested to play a role in multiple forms of insulin resistance 13 14 . |
| 6081 | INS | insulin | insulin | 1.0 | gulated systemically in the skeletal muscle 9 10 adipose tissue 11 and peripheral blood mononuclear cells 17 of patients with type 2 diabetes suggesting that the oxphos pathway plays a causal role in insulin resistance in type 2 diabetes 18 . |
| 4552 | GPT | glutamic-pyruvate transaminase (alanine aminotransferase) | alanine aminotransferase | 1.0 | bmi and alanine aminotransferase values were elevated significantly in the overweight group p _lt_ 0.05 . |
| 336 | AGTR1 | angiotensin II receptor, type 1 | angiotensin ii receptor | 1.0 | pharmacological treatments did not include statins angiotensin converting enzyme inhibitors or angiotensin ii receptor blockers. |
| 6081 | INS | insulin | insulin | 1.0 | none was prescribed any oral hypoglycemic agent or basal insulin replacement. |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | angiotensin converting enzyme | 1.0 | pharmacological treatments did not include statins angiotensin converting enzyme inhibitors or angiotensin ii receptor blockers. |