Interleukin-6 deficiency facilitates myocardial dysfunction during high fat diet-induced obesity by promoting lipotoxicity and inflammation

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1863

Article

Chen, Fan¹  Chen, Dandan¹  Zhao, Xinmei¹  Yang, Shuai¹  Li, Zhe^2,3,4  Sanchis, Daniel⁵  Jin, Liang¹  Qiang, Xizhe¹  Wang, Kaiye¹  Xu, Yitao¹  Zhang, Yubin¹  Ye, Junmei¹ 

[1] China Pharmaceut Univ, Sch Life Sci & Technol, Dept Biochem, State Key Lab Nat Med, Nanjing 210006, Jiangsu, Peoples R China

[2] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Hubei, Peoples R China

[3] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Hubei, Peoples R China

[4] Hubei Key Lab Cardiol, Wuhan 430060, Hubei, Peoples R China

[5] Univ Lleida, Inst Recerca Biomed Lleida IRBLleida, Edifici Biomed 1,Av Rovira Roure 80, Lleida 25198, Spain

关键词: Interleukin-6 (IL-6);    Fatty acids;    Lipotoxicity;    Inflammation;    Cardiac dysfunction;    High fat diet;   

DOI  :  10.1016/j.bbadis.2017.08.022

来源: Elsevier

【 摘 要 】

Objective: Obesity is associated with metabolic disorder and chronic inflammation that plays a crucial role in cardiovascular diseases. IL-6 is involved in regulating obesity-related lipid metabolism and inflammation. In this study, we sought to determine the role of IL-6 in high-fat diet (HFD)-induced cardiomyopathy and explore the signaling pathway. Methods: Female, 5-week-old IL-6 knockout (KO) and littermate mice were fed a normal diet (ND, 10% fat) or HFD (45% fat) for 14 weeks. At the end of treatment, cardiac function was assessed by echocardiography. Adipose tissues and plasma were collected for further measurement. Immunohistology of CD68 was performed to detect inflammation in the heart. Masson's trichrome staining and Oil Red O staining was applied to evaluated cardiac fibrosis and lipid accumulation. Real-time PCR and Western immunoblotting analyses on heart tissue were used to explore the underlying mechanism. Results: IL-6 KO mice displayed increased insulin resistance compared to WT mice at baseline. When fed HFD, IL-6 KO mice showed decreased gains in body weight and fat mass, increased insulin resistance relative to IL-6 KO mice feed ND. Furthermore, IL-6 KO mice developed cardiac dysfunction during HFD-induced obesity. Histological analysis suggested increased lipid accumulation, fibrosis and inflammation without affecting cardiac morphology during HFD treatment in the heart of IL-6 KO mice. Finally, IL-6 deficiency increased the phosphorylation of AMPK and ACC in the heart during HFD-induced obesity. Conclusion: Our results suggest that IL-6 contributes to limit lipid metabolic disorder, cardiac hypertrophy, fibrosis, inflammation and myocardium lipotoxicity during HFD-induced obesity.

【 授权许可】

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