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MD2 may be a new target for the treatment of obesity‐induced cardiac injury
Author(s) -
Qian Yuanyuan,
Zhong Peng,
Wang Yi,
Liang Guang
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.964.5
Subject(s) - inflammation , medicine , pathogenesis , fibrosis , oxidative stress , endocrinology , tlr4 , cardiac fibrosis , pharmacology
Background Obesity is strongly associated with cardiovascular diseases. Accumulating evidences have demonstrated a vital role of TLR4 signaling in the pathogenesis of obesity‐induced complications. Myeloid differentiation 2 (MD2), an obligate partner for TLR4, was required for LPS‐associated inflammation and TLR4 signaling activation. However, whether MD2 is also involved in the obesity‐associated inflammation is still unknown. The aim of this study is to investigate the involvement of MD2 in the pathogenesis of obesity‐induced cardiac diseases. Methods Cardiac H9C2 cells exposed to free fatty acid were pretreated L6H9, a specific MD2 inhibitor or MD2 silencing siRNA. Rats and APOE ‐/‐ mice were given high fat diet for eight weeks and administrated with L6H9 by daily gavage. Results In H9C2 cells, FFA was found to induce inflammation, oxidative stress, ER stress, mitochondrial dysfunction, and ultimately cardiac hypertrophy, fibrosis, and apoptosis. Interestingly, all these alterations were significantly inhibited by pharmacological inhibition and genetic silence of MD2. In vivo, two obese models markedly induced cardiac inflammation and oxidative stress and ultimately lead to cardiac remodeling including cardiac disorganization, hypertrophy, apoptosis and fibrosis. All these molecular and pathological alterations were remarkably attenuated by the administration with MD2 inhibitors. Conclusion MD2 is involved in the pathogenesis of obesity‐associated cardiac remodeling via mediating FFA‐induced inflammation, and MD2 can be a therapeutic target in treating obesity‐induced complications.