HIF1A and PPARG in hypertrophic cardiomyopathy (WP2456)
Homo sapiens
The genes hypoxia-inducible factor 1A and peroxisome proliferator activated receptor gamma play a role in regulating glycolysis, triacylglyceride synthesis, and ultimately hypertrophic cardiomyopathy. This diagram is derived from Figure 6D in PMID:19490906: “Schematic representation of the coregulation of glycolysis and glycerolipid synthesis by HIF1A. Hypertrophy-induced HIF1A accumulation is predicted to simultaneously promote the transcriptional upregulation of glycolytic enzymes and the direct transcriptional activation of the PPARG promoter. PPARG activity would lead to the upregulation of its target genes, GPD1 and GPAT, leading to promotion of glycerolipid biosynthesis, culminating in TAG accumulation. A secondary level of coordination is predicted to occur via the shuttling of NADH and NAD+ between GAPDH and GPD1. Thus, coordinated regulation of both these components by HIF1A is hypothesized to favor cardiomyocyte lipid accumulation in hypertrophy.” This pathway is part the CPTAC Assay Portal.
Authors
M Aguirre , Jonathan Mélius , Chris Evelo , Kristina Hanspers , Friederike Ehrhart , Alex Pico , Finterly Hu , Eric Weitz , and Egon WillighagenActivity
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Cited In
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Organisms
Homo sapiensCommunities
ONTOXAnnotations
Pathway Ontology
lipid metabolic pathway regulatory pathway glycolysis/gluconeogenesis pathwayCell Type Ontology
cardiac muscle cellDisease Ontology
hypertrophic cardiomyopathy| Label | Type | Compact URI | Comment |
|---|---|---|---|
| Glyceraldehyde-3-phosphate | Metabolite | kegg.compound:C00118 | |
| Pyruvate | Metabolite | kegg.compound:C00022 | |
| Fructose-1,6-biphosphate | Metabolite | kegg.compound:C05378 | |
| Dihydroxyacetonephosphate | Metabolite | kegg.compound:C00111 | |
| Lactate | Metabolite | kegg.compound:C00186 | |
| Glycerol-3-phosphate | Metabolite | kegg.compound:C00093 | |
| Lysophosphatidate | Metabolite | kegg.compound:C00681 | |
| Triacylglycerol | Metabolite | kegg.compound:C00422 | |
| Diacylglycerol | Metabolite | kegg.compound:C00165 | |
| Glucose | Metabolite | kegg.compound:C00031 | |
| Fatty acid | Metabolite | chebi:35366 | |
| NADH | Metabolite | chebi:16908 | |
| NAD+ | Metabolite | chebi:15846 | |
| H+ | Metabolite | chebi:49637 | |
| Pi | Metabolite | chebi:28659 | |
| Acetyl-CoA | Metabolite | chebi:49637 | |
| CoA-SH | Metabolite | chebi:15346 | |
| GAPDH | GeneProduct | ensembl:ENSG00000111640 | |
| LDHA | GeneProduct | ensembl:ENSG00000134333 | |
| TPI1 | GeneProduct | ensembl:ENSG00000111669 | |
| GPD1 | GeneProduct | ensembl:ENSG00000167588 | |
| GPAT3 | GeneProduct | ensembl:ENSG00000138678 | |
| SLC2A1 | GeneProduct | ensembl:ENSG00000117394 | |
| PPARG | GeneProduct | ensembl:ENSG00000132170 | |
| HIF1A | GeneProduct | ensembl:ENSG00000100644 | |
| CD36 | GeneProduct | ensembl:ENSG00000135218 |
References
- Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Krishnan J, Suter M, Windak R, Krebs T, Felley A, Montessuit C, et al. Cell Metab. 2009 Jun;9(6):512–24. PubMed Europe PMC Scholia