PUBLICATION
Deficiency of Adipose Triglyceride Lipase Induces Metabolic Syndrome and Cardiomyopathy in Zebrafish
- Authors
- Lai, H.H., Yeh, K.Y., Hsu, H.M., Her, G.M.
- ID
- ZDB-PUB-230109-10
- Date
- 2022
- Source
- International Journal of Molecular Sciences 24(1): (Journal)
- Registered Authors
- Her, Guor Muor
- Keywords
- cardiomyopathy, lipid metabolism, lipolysis, metabolic syndrome
- MeSH Terms
-
- Adipose Tissue/metabolism
- Animals
- CRISPR-Associated Protein 9/metabolism
- Cardiomyopathies*/genetics
- Cardiomyopathies*/metabolism
- Lipase/genetics
- Lipase/metabolism
- Lipolysis/genetics
- Metabolic Syndrome*/metabolism
- Triglycerides/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 36613558 Full text @ Int. J. Mol. Sci.
Citation
Lai, H.H., Yeh, K.Y., Hsu, H.M., Her, G.M. (2022) Deficiency of Adipose Triglyceride Lipase Induces Metabolic Syndrome and Cardiomyopathy in Zebrafish. International Journal of Molecular Sciences. 24(1):.
Abstract
Lipid metabolism dysfunction is related to clinical disorders including obesity, cancer, liver steatosis, and cardiomyopathy. Impaired lipolytic enzymes result in altered release of free fatty acids. The dramatic change in dyslipidemia is important in lipotoxic cardiomyopathy. Adipose triglyceride lipase (ATGL) catalyzes the lipolysis of triacylglycerol to reduce intramyocardial triglyceride levels in the heart and improve myocardial function. We examined the role of ATGL in metabolic cardiomyopathy by developing an Atgl knockout (ALKO) zebrafish model of metabolic cardiomyopathy disease by continuously expressing CRISPR/Cas9 protein and atgl gene guide RNAs (gRNAs). The expressed Cas9 protein bound to four gRNAs targeting the atgl gene locus, facilitating systemic gene KO. Ablation of Atgl interfered with lipid metabolism, which induced hyperlipidemia and hyperglycemia. ALKO adults and embryos displayed hypertrophic hearts. ALKO presented a typical dilated cardiomyopathy profile with a remarkable reduction in four sarcomere genes (myosin heavy chain 7-like,actin alpha cardiac muscle 1b,myosin binding protein C3, and troponin T type 2a) and two Ca2+ handling regulator genes (tropomyosin 4b and ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2b). Immune cell infiltration in cardiac tissue of ALKO provided direct evidence of advanced metabolic cardiomyopathy. The presently described model could become a powerful tool to clarify the underlying mechanism between metabolic disorders and cardiomyopathies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping