General Information:

Id: 889
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Rattus norvegicus
male
PGC-1beta ASO: knockdown of expression of PGC-1beta using antisense ologonucleotides (ASO)
article
Reference: Nagai Y et al.(2009) The role of peroxisome proliferator-activated receptor gamma coactivator-1 beta in the pathogenesis of fructose-induced insulin resistance. Cell Metab. 9: 252-264 [PMID: 19254570]

Interaction Information:

Comment Compared with the rats fed high-fructose diet, the plasma glucose and insulin levels were significantly lower in PGC-1beta ASO-treated rats, 12% and 37%, respectively. The plasma triglyceride and leptin levels and epididymal fat mass were also significantly lower: 40%, 50%, and 13%, respectively. On the other hand, plasma concentrations of total cholesterol, HDL cholesterol, and beta-hydroxybutyrate were significantly higher in PGC-1beta ASO-treated rats: 58%, 63%, and 11%, respectively. Finally, there were no differences in plasma concentrations of glucagon, adiponectin, or retinol-binding protein 4 (RBP4).
Formal Description
Interaction-ID: 5241

gene/protein

PPARGC1B

affects_quantity of

drug/chemical compound

Glucose

in blood; if PPARGC1B expression is knocked down
Comment PGC-1beta ASO inhibited the synthesis of fatty acids but not of cholesterol.
Formal Description
Interaction-ID: 5242

gene/protein

PPARGC1B

affects_activity of

if PPARGC1B expression is knocked down
Comment PGC-1beta ASO inhibited the synthesis of fatty acids but not of cholesterol.
Formal Description
Interaction-ID: 5244

gene/protein

PPARGC1B

NOT affects_activity of

if PPARGC1B expression is knocked down
Comment The decreased lipid synthesis in vitro was reflected in vivo, where PGC-1beta ASO prevented the accumulation of liver triglyceride observed with high-fructose feeding.
Formal Description
Interaction-ID: 5245

gene/protein

PPARGC1B

NOT affects_quantity of

drug/chemical compound

Triacylglycerol

in liver; after high-fructose diet, if PPARGC1B expression is knocked down
Comment PGC-1beta ASO improved the metabolic phenotype induced by fructose feeding by reducing expression of SREBP-1 and downstream lipogenic genes in liver.
Formal Description
Interaction-ID: 5247

gene/protein

PPARGC1B

affects_expression of

gene/protein

SREBF1

in liver; after high-fructose diet, if PPARGC1B expression is knocked down
Comment PGC-1beta ASO improved the metabolic phenotype induced by fructose feeding by reducing expression of SREBP-1 and downstream lipogenic genes in liver.
Formal Description
Interaction-ID: 5250

gene/protein

PPARGC1B

affects_activity of

in liver; after high-fructose diet, if PPARGC1B expression is knocked down
Comment PGC-1beta ASO protects high-fructose-fed but not regular chow-fed rats from hepatic insulin resistance.
Formal Description
Interaction-ID: 5252

gene/protein

PPARGC1B

affects_activity of

disease

Insulin resistance

in liver; after high-fructose diet, if PPARGC1B expression is knocked down
Comment PGC-1beta ASO protects high-fructose-fed but not regular chow-fed rats from hepatic insulin resistance.
Formal Description
Interaction-ID: 5253

gene/protein

PPARGC1B

NOT affects_activity of

disease

Insulin resistance

in liver; after regular chow diet, if PPARGC1B expression is knocked down
Comment Insulin-stimulated whole-body glucose disposal was decreased by about 50% in the high-fructose-fed rats compared to the regular chow-fed rats. PGC-1beta ASO rescued the fructose-induced insulin resistance, as shown by the 90% increase in insulin-stimulated whole-body glucose uptake.
Formal Description
Interaction-ID: 5254

environment

high-fructose diet

increases_activity of

disease

Insulin resistance

Comment Examination of the gene expression of PPAR-gamma and its target genes in epididymal white adipose tissue revealed that in comparison to wild-type mice, the expression of PPAR-gamma was decreased by 50%, and adipocyte protein 2 (aP2), adiponectin, and acyl-CoA synthetases (ACS) were decreased in PGC-1beta ASO-treated groups.
Formal Description
Interaction-ID: 5287

gene/protein

PPARGC1B

affects_expression of

gene/protein

PPARG

if PPARGC1B expression is knocked down
Drugbank entries Show/Hide entries for PPARG
Comment PGC-1beta also induces mRNA expression of GLUT4 in cultures of primary rat skeletal muscle cells. In the present study, GLUT4 mRNA in WAT was decreased by 50% in PGC-1beta ASO-treated groups compared to wild-type mice. In contrast, the protein expression in both total tissue lysate and plasma membrane was increased 2-fold in only PGC-1beta ASO-treated high-fructose-fed rats, consistent with the result of 2-deoxyglucose uptake in WAT. There were no differences in the expression of other glucose transporters, GLUT1 and GLUT5 (known as a fructose transporter).
Formal Description
Interaction-ID: 5289

gene/protein

PPARGC1B

increases_expression of

gene/protein

SLC2A4

Comment Interestingly, the amelioration of diet-induced insulin resistance by PGC-1beta ASO was not seen in high-fat-fed rats. Consistent with this result, GLUT4 protein expressionin WAT was not increased in high-fat-fed rats.
Formal Description
Interaction-ID: 5291

gene/protein

PPARGC1B

NOT decreases_activity of

disease

Insulin resistance

after high-fat diet, if PPARGC1B expression is knocked down
Comment Hepatic de novo lipogenesis and hepatic triglyceride synthesis induced by fructose are both decreased by PGC-1beta ASO treatment.
Formal Description
Interaction-ID: 5297

gene/protein

PPARGC1B

affects_activity of

in liver; induced by fructose, if PPARGC1B expression is knocked down
Comment Hepatic de novo lipogenesis and hepatic triglyceride synthesis induced by fructose are both decreased by PGC-1beta ASO treatment.
Formal Description
Interaction-ID: 5298

gene/protein

PPARGC1B

affects_activity of

in liver; induced by fructose, if PPARGC1B expression is knocked down
Comment Knockdown of PGC-1beta prevents fructose-induced hypertriglyceridemia and hepatic and peripheral insulin resistance.
Formal Description
Interaction-ID: 5299

gene/protein

PPARGC1B

affects_activity of

disease

Insulin resistance

in liver, in skeletal muscle, in white adipose tissue; induced by fructose, if PPARGC1B expression is knocked down
Comment PGC-1beta ASO increased insulin-stimulated whole-body glucose disposal due to a threefold increase in glucose uptake in white adipose tissue.
Formal Description
Interaction-ID: 5301

gene/protein

PPARGC1B

affects_activity of

process

glucose import

in white adipose tissue; stimulated by insulin, if PPARGC1B expression is knocked down
Comment Compared with the rats fed high-fructose diet, the plasma glucose and insulin levels were significantly lower in PGC-1beta ASO-treated rats, 12% and 37%, respectively. The plasma triglyceride and leptin levels and epididymal fat mass were also significantly lower: 40%, 50%, and 13%, respectively. On the other hand, plasma concentrations of total cholesterol, HDL cholesterol, and beta-hydroxybutyrate were significantly higher in PGC-1beta ASO-treated rats: 58%, 63%, and 11%, respectively. Finally, there were no differences in plasma concentrations of glucagon, adiponectin, or retinol-binding protein 4 (RBP4).
Formal Description
Interaction-ID: 13149

gene/protein

PPARGC1B

affects_quantity of

complex/PPI

Insulin

in blood; if PPARGC1B expression is knocked down
Comment Compared with the rats fed high-fructose diet, the plasma glucose and insulin levels were significantly lower in PGC-1beta ASO-treated rats, 12% and 37%, respectively. The plasma triglyceride and leptin levels and epididymal fat mass were also significantly lower: 40%, 50%, and 13%, respectively. On the other hand, plasma concentrations of total cholesterol, HDL cholesterol, and beta-hydroxybutyrate were significantly higher in PGC-1beta ASO-treated rats: 58%, 63%, and 11%, respectively. Finally, there were no differences in plasma concentrations of glucagon, adiponectin, or retinol-binding protein 4 (RBP4).
Formal Description
Interaction-ID: 13150

gene/protein

PPARGC1B

affects_quantity of

drug/chemical compound

Triacylglycerol

in blood; if PPARGC1B expression is knocked down
Comment Compared with the rats fed high-fructose diet, the plasma glucose and insulin levels were significantly lower in PGC-1beta ASO-treated rats, 12% and 37%, respectively. The plasma triglyceride and leptin levels and epididymal fat mass were also significantly lower: 40%, 50%, and 13%, respectively. On the other hand, plasma concentrations of total cholesterol, HDL cholesterol, and beta-hydroxybutyrate were significantly higher in PGC-1beta ASO-treated rats: 58%, 63%, and 11%, respectively. Finally, there were no differences in plasma concentrations of glucagon, adiponectin, or retinol-binding protein 4 (RBP4).
Formal Description
Interaction-ID: 13151

gene/protein

PPARGC1B

affects_quantity of

gene/protein

LEP

in blood; if PPARGC1B expression is knocked down
Comment Compared with the rats fed high-fructose diet, the plasma glucose and insulin levels were significantly lower in PGC-1beta ASO-treated rats, 12% and 37%, respectively. The plasma triglyceride and leptin levels and epididymal fat mass were also significantly lower: 40%, 50%, and 13%, respectively. On the other hand, plasma concentrations of total cholesterol, HDL cholesterol, and beta-hydroxybutyrate were significantly higher in PGC-1beta ASO-treated rats: 58%, 63%, and 11%, respectively. Finally, there were no differences in plasma concentrations of glucagon, adiponectin, or retinol-binding protein 4 (RBP4).
Formal Description
Interaction-ID: 13152

gene/protein

PPARGC1B

affects_quantity of

drug/chemical compound

Cholesterol

in blood; if PPARGC1B expression is knocked down
Drugbank entries Show/Hide entries for
Comment Compared with the rats fed high-fructose diet, the plasma glucose and insulin levels were significantly lower in PGC-1beta ASO-treated rats, 12% and 37%, respectively. The plasma triglyceride and leptin levels and epididymal fat mass were also significantly lower: 40%, 50%, and 13%, respectively. On the other hand, plasma concentrations of total cholesterol, HDL cholesterol, and beta-hydroxybutyrate were significantly higher in PGC-1beta ASO-treated rats: 58%, 63%, and 11%, respectively. Finally, there were no differences in plasma concentrations of glucagon, adiponectin, or retinol-binding protein 4 (RBP4).
Formal Description
Interaction-ID: 13153

gene/protein

PPARGC1B

affects_activity of

if PPARGC1B expression is knocked down
Comment Compared with the rats fed high-fructose diet, the plasma glucose and insulin levels were significantly lower in PGC-1beta ASO-treated rats, 12% and 37%, respectively. The plasma triglyceride and leptin levels and epididymal fat mass were also significantly lower: 40%, 50%, and 13%, respectively. On the other hand, plasma concentrations of total cholesterol, HDL cholesterol, and beta-hydroxybutyrate were significantly higher in PGC-1beta ASO-treated rats: 58%, 63%, and 11%, respectively. Finally, there were no differences in plasma concentrations of glucagon, adiponectin, or retinol-binding protein 4 (RBP4).
Formal Description
Interaction-ID: 13154

gene/protein

PPARGC1B

affects_quantity of

drug/chemical compound

(R)-3-Hydroxybutanoate

if PPARGC1B expression is knocked down
Comment Compared with the rats fed high-fructose diet, the plasma glucose and insulin levels were significantly lower in PGC-1beta ASO-treated rats, 12% and 37%, respectively. The plasma triglyceride and leptin levels and epididymal fat mass were also significantly lower: 40%, 50%, and 13%, respectively. On the other hand, plasma concentrations of total cholesterol, HDL cholesterol, and beta-hydroxybutyrate were significantly higher in PGC-1beta ASO-treated rats: 58%, 63%, and 11%, respectively. Finally, there were no differences in plasma concentrations of glucagon, adiponectin, or retinol-binding protein 4 (RBP4).
Formal Description
Interaction-ID: 13155

gene/protein

PPARGC1B

NOT affects_quantity of

gene/protein

Glucagon

if PPARGC1B expression is knocked down
Comment Compared with the rats fed high-fructose diet, the plasma glucose and insulin levels were significantly lower in PGC-1beta ASO-treated rats, 12% and 37%, respectively. The plasma triglyceride and leptin levels and epididymal fat mass were also significantly lower: 40%, 50%, and 13%, respectively. On the other hand, plasma concentrations of total cholesterol, HDL cholesterol, and beta-hydroxybutyrate were significantly higher in PGC-1beta ASO-treated rats: 58%, 63%, and 11%, respectively. Finally, there were no differences in plasma concentrations of glucagon, adiponectin, or retinol-binding protein 4 (RBP4).
Formal Description
Interaction-ID: 13156

gene/protein

PPARGC1B

NOT affects_quantity of

gene/protein

ADIPOQ

if PPARGC1B expression is knocked down
Comment Compared with the rats fed high-fructose diet, the plasma glucose and insulin levels were significantly lower in PGC-1beta ASO-treated rats, 12% and 37%, respectively. The plasma triglyceride and leptin levels and epididymal fat mass were also significantly lower: 40%, 50%, and 13%, respectively. On the other hand, plasma concentrations of total cholesterol, HDL cholesterol, and beta-hydroxybutyrate were significantly higher in PGC-1beta ASO-treated rats: 58%, 63%, and 11%, respectively. Finally, there were no differences in plasma concentrations of glucagon, adiponectin, or retinol-binding protein 4 (RBP4).
Formal Description
Interaction-ID: 13157

gene/protein

PPARGC1B

NOT affects_quantity of

gene/protein

RBP4

if PPARGC1B expression is knocked down
Comment Insulin-stimulated whole-body glucose disposal was decreased by about 50% in the high-fructose-fed rats compared to the regular chow-fed rats. PGC-1beta ASO rescued the fructose-induced insulin resistance, as shown by the 90% increase in insulin-stimulated whole-body glucose uptake.
Formal Description
Interaction-ID: 13158

gene/protein

PPARGC1B

affects_activity of

disease

Insulin resistance

if insulin resistance is induced by high-fructose diet and if PPARGC1B expression is knocked down
Comment Examination of the gene expression of PPAR-gamma and its target genes in epididymal white adipose tissue revealed that in comparison to wild-type mice, the expression of PPAR-gamma was decreased by 50%, and adipocyte protein 2 (aP2), adiponectin, and acyl-CoA synthetases (ACS) were decreased in PGC-1beta ASO-treated groups.
Formal Description
Interaction-ID: 13159

gene/protein

PPARGC1B

affects_expression of

gene/protein

FABP4

if PPARGC1B expression is knocked down
Comment Examination of the gene expression of PPAR-gamma and its target genes in epididymal white adipose tissue revealed that in comparison to wild-type mice, the expression of PPAR-gamma was decreased by 50%, and adipocyte protein 2 (aP2), adiponectin, and acyl-CoA synthetases (ACS) were decreased in PGC-1beta ASO-treated groups.
Formal Description
Interaction-ID: 13164

gene/protein

PPARGC1B

affects_expression of

gene/protein

ACS

if PPARGC1B expression is knocked down
Drugbank entries Show/Hide entries for ACS
Comment PGC-1beta also induces mRNA expression of GLUT4 in cultures of primary rat skeletal muscle cells. In the present study, GLUT4 mRNA in WAT was decreased by 50% in PGC-1beta ASO-treated groups compared to wild-type mice. In contrast, the protein expression in both total tissue lysate and plasma membrane was increased 2-fold in only PGC-1beta ASO-treated high-fructose-fed rats, consistent with the result of 2-deoxyglucose uptake in WAT. There were no differences in the expression of other glucose transporters, GLUT1 and GLUT5 (known as a fructose transporter).
Formal Description
Interaction-ID: 13167

gene/protein

PPARGC1B

NOT affects_expression of

gene/protein

SLC2A1

Comment PGC-1beta also induces mRNA expression of GLUT4 in cultures of primary rat skeletal muscle cells. In the present study, GLUT4 mRNA in WAT was decreased by 50% in PGC-1beta ASO-treated groups compared to wild-type mice. In contrast, the protein expression in both total tissue lysate and plasma membrane was increased 2-fold in only PGC-1beta ASO-treated high-fructose-fed rats, consistent with the result of 2-deoxyglucose uptake in WAT. There were no differences in the expression of other glucose transporters, GLUT1 and GLUT5 (known as a fructose transporter).
Formal Description
Interaction-ID: 13168

gene/protein

PPARGC1B

NOT affects_expression of

gene/protein

SLC2A5