General Information:

Id: 824 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Obesity - [OMIM]
Mammalia
review
Reference: Sugden MC et al.(2010) PPAR control: its SIRTainly as easy as PGC J. Endocrinol. 2: 93-104 [PMID: 19770177]

Interaction Information:

Comment Certain PPAR-gamma target genes that are normally expressed only at low levels in mature adipocytes are dramatically upregulated by thiazolidinediones (TZDs), among these the enzyme glycerol kinase. Glycerol kinase allows glycerol 3-phosphate production from glycerol, thereby enhancing the capacity for FA esterification to TAG.
Formal Description
Interaction-ID: 5026

drug/chemical compound

Thiazolidinedione

increases_expression of

gene/protein

GK

Comment Unlike classic PPAR-gamma-target genes such as aP2 (which is constitutively associated with coactivators), the glycerol kinase gene is targeted by NR corepressors. TZDs trigger the dismissal of corepressor HDAC complexes and the recruitment of coactivators to the glycerol kinase gene. They also induce PGC-1alpha, whose recruitment to the glycerol kinase gene is sufficient to release the corepressors.
Formal Description
Interaction-ID: 5031

drug/chemical compound

Thiazolidinedione

affects_activity of

gene/protein

GK

Comment In ob/ob mice, the expression of transcripts encoding mitochondrial proteins decreases with the development of obesity. TZD treatment in ob/ob mice increases PGC-1alpha expression and increases mitochondrial mass and energy expenditure.
Formal Description
Interaction-ID: 5041

drug/chemical compound

Thiazolidinedione

increases_expression of

gene/protein

PPARGC1A

Comment Alterations in lipin-1 function in adipose tissue are likely to impact the efficacy of the TZDs in the treatment of insulin resistance. The expression of the lipin-1 isoform found in mature adipocytes (lipin-1beta) increases following TZD treatment, which causes weight gain.
Formal Description
Interaction-ID: 5127

drug/chemical compound

Thiazolidinedione

increases_expression of

mRNA/protein variant

LPIN1B

in adipose tissue, in mature adipocytes
Comment Alterations in lipin-1 function in adipose tissue are likely to impact the efficacy of the TZDs in the treatment of insulin resistance. The expression of the lipin-1 isoform found in mature adipocytes (lipin-1beta) increases following TZD treatment, which causes weight gain.
Formal Description
Interaction-ID: 5128

drug/chemical compound

Thiazolidinedione

increases_activity of

Comment Unlike classic PPAR-gamma-target genes such as aP2 (which is constitutively associated with coactivators), the glycerol kinase gene is targeted by NR corepressors. TZDs trigger the dismissal of corepressor HDAC complexes and the recruitment of coactivators to the glycerol kinase gene. They also induce PGC-1alpha, whose recruitment to the glycerol kinase gene is sufficient to release the corepressors.
Formal Description
Interaction-ID: 13117

drug/chemical compound

Thiazolidinedione

affects_activity of

gene/protein

PPARGC1A