RRC ID 49602
Author Fang Q, Wang J, Zhang Y, Wang L, Li W, Han J, Huang W, Liang G, Wang Y.
Title Inhibition of myeloid differentiation factor-2 attenuates obesity-induced cardiomyopathy and fibrosis.
Journal Biochim Biophys Acta Mol Basis Dis
Abstract Obesity causes cardiovascular diseases, including cardiac hypertrophy and remodeling, via chronic tissue inflammation. Myeloid differentiation factor-2 (MD2), a binding protein of lipopolysaccharide, is functionally essential for the activation of proinflammatory pathways in endotoxin-induced acute inflammatory diseases. Here we tested the hypothesis that MD2 plays a central role in obesity-induced cardiomyopathy. Wildtype or MD2 knockout mice were fed with a high fat diet (HFD) or normal diet (Control) for total 16weeks, and MD2 inhibitor L6H21 (20mg/kg) or vehicle (1% CMC-Na) were administered from the beginning of the 9th week. HFD induced significant weight gain and cardiac hypertrophy, with increased cardiac fibrosis and inflammation. L6H21 administration or MD2 knockout attenuated HFD-induced obesity, inflammation and cardiac remodeling. In vitro exposure of H9C2 cells to high lipids induced cell hypertrophy with activated JNK/ERK and NF-κB pathways, which was abolished by pretreatment of MD2 inhibitor L6H21. Our results demonstrate that MD2 is essential to obesity-related cardiac hypertrophy through activating JNK/ERK and NF-κB-dependent cardiac inflammatory pathways. Targeting MD2 would be a therapeutic approach to prevent obesity-induced cardiac injury and remodeling.
Volume 1864(1)
Pages 252-262
Published 2018-1-1
DOI 10.1016/j.bbadis.2017.09.026
PII S0925-4439(17)30352-6
PMID 28965884
MeSH Animals Animals, Newborn Cardiomegaly / pathology Cardiomegaly / prevention & control Cardiomyopathies / etiology Cardiomyopathies / prevention & control* Cardiotonic Agents / pharmacology* Cells, Cultured Chalcones / pharmacology* Diet, High-Fat Fibrosis / prevention & control Heart / drug effects* Lymphocyte Antigen 96 / antagonists & inhibitors* Lymphocyte Antigen 96 / genetics Male Mice Mice, Inbred C57BL Mice, Knockout Myocardium / pathology* Myocytes, Cardiac / drug effects Myocytes, Cardiac / metabolism Myocytes, Cardiac / pathology Obesity / complications* Rats
IF 4.328
Times Cited 4
Mice RBRC02388