PUBLICATION
A network-based approach to identify deregulated pathways and drug effects in metabolic syndrome
- Authors
- Misselbeck, K., Parolo, S., Lorenzini, F., Savoca, V., Leonardelli, L., Bora, P., Morine, M.J., Mione, M.C., Domenici, E., Priami, C.
- ID
- ZDB-PUB-191120-5
- Date
- 2019
- Source
- Nature communications 10: 5215 (Journal)
- Registered Authors
- Mione, Marina
- Keywords
- none
- MeSH Terms
-
- Animals
- Diet, High-Fat
- Drug Repositioning
- Gene Regulatory Networks*/drug effects
- Humans
- Lipid Metabolism/drug effects
- Macrophages/drug effects
- Macrophages/metabolism
- Metabolic Syndrome/drug therapy
- Metabolic Syndrome/genetics*
- Organ Specificity/genetics
- Pharmaceutical Preparations/metabolism*
- Pyrazoles/pharmacology
- Pyrazoles/therapeutic use
- Pyrimidines/pharmacology
- Pyrimidines/therapeutic use
- Reproducibility of Results
- Signal Transduction/genetics*
- Zebrafish/metabolism
- PubMed
- 31740673 Full text @ Nat. Commun.
Citation
Misselbeck, K., Parolo, S., Lorenzini, F., Savoca, V., Leonardelli, L., Bora, P., Morine, M.J., Mione, M.C., Domenici, E., Priami, C. (2019) A network-based approach to identify deregulated pathways and drug effects in metabolic syndrome. Nature communications. 10:5215.
Abstract
Metabolic syndrome is a pathological condition characterized by obesity, hyperglycemia, hypertension, elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol that increase cardiovascular disease risk and type 2 diabetes. Although numerous predisposing genetic risk factors have been identified, the biological mechanisms underlying this complex phenotype are not fully elucidated. Here we introduce a systems biology approach based on network analysis to investigate deregulated biological processes and subsequently identify drug repurposing candidates. A proximity score describing the interaction between drugs and pathways is defined by combining topological and functional similarities. The results of this computational framework highlight a prominent role of the immune system in metabolic syndrome and suggest a potential use of the BTK inhibitor ibrutinib as a novel pharmacological treatment. An experimental validation using a high fat diet-induced obesity model in zebrafish larvae shows the effectiveness of ibrutinib in lowering the inflammatory load due to macrophage accumulation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping