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

被引:34
作者
Chen, Fan [1 ]
Chen, Dandan [1 ]
Zhao, Xinmei [1 ]
Yang, Shuai [1 ]
Li, Zhe [2 ,3 ,4 ]
Sanchis, Daniel [5 ]
Jin, Liang [1 ]
Qiang, Xizhe [1 ]
Wang, Kaiye [1 ]
Xu, Yitao [1 ]
Zhang, Yubin [1 ]
Ye, Junmei [1 ]
机构
[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
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2017年 / 1863卷 / 12期
基金
中国国家自然科学基金; 国家高技术研究发展计划(863计划);
关键词
Interleukin-6 (IL-6); Fatty acids; Lipotoxicity; Inflammation; Cardiac dysfunction; High fat diet; CARDIAC MYOCYTES; UP-REGULATION; OXIDATIVE STRESS; BODY-WEIGHT; PPAR-ALPHA; HEART; ADIPONECTIN; METABOLISM; HYPERTROPHY; EXPRESSION;
D O I
10.1016/j.bbadis.2017.08.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
引用
收藏
页码:3128 / 3141
页数:14
相关论文
共 69 条
[1]   CONTRIBUTION OF OXIDATIVE-METABOLISM AND GLYCOLYSIS TO ATP PRODUCTION IN HYPERTROPHIED HEARTS [J].
ALLARD, MF ;
SCHONEKESS, BO ;
HENNING, SL ;
ENGLISH, DR ;
LOPASCHUK, GD .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 267 (02) :H742-H750
[2]   The Role of Adipose Tissue and Adipokines in Obesity-Related Inflammatory Diseases [J].
Balistreri, Carmela Rita ;
Caruso, Calogero ;
Candore, Giuseppina .
MEDIATORS OF INFLAMMATION, 2010, 2010
[3]   Interleukin 6 modulates PPARα and PGC-1α and is involved in high-fat diet induced cardiac lipotoxicity in mouse [J].
Bonda, Tomasz A. ;
Szynaka, Beata ;
Sokolowska, Magdalena ;
Dziemidowicz, Magdalena ;
Winnicka, Maria M. ;
Bernaczyk, Piotr ;
Wawrusiewicz-Kurylonek, Natalia ;
Kaminski, Karol A. .
INTERNATIONAL JOURNAL OF CARDIOLOGY, 2016, 219 :1-8
[4]   Oxidative stress and inflammation interactions in human obesity [J].
Bondia-Pons, Isabel ;
Ryan, Lisa ;
Alfredo Martinez, J. .
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY, 2012, 68 (04) :701-711
[5]   Diabetic cardiomyopathy revisited [J].
Boudina, Sihem ;
Abel, E. Dale .
CIRCULATION, 2007, 115 (25) :3213-3223
[6]   CARD9 knockout ameliorates myocardial dysfunction associated with high fat diet-induced obesity [J].
Cao, Li ;
Qin, Xing ;
Peterson, Matthew R. ;
Haller, Samantha E. ;
Wilson, Kayla A. ;
Hu, Nan ;
Lin, Xin ;
Nair, Sreejayan ;
Ren, Jun ;
He, Guanglong .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2016, 92 :185-195
[7]  
Chabowski A, 2007, J PHYSIOL PHARMACOL, V58, P73
[8]   A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids [J].
Chavez, JA ;
Knotts, TA ;
Wang, LP ;
Li, GB ;
Dobrowsky, RT ;
Florant, GL ;
Summers, SA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (12) :10297-10303
[9]   Role of diet and fuel overabundance in the development and progression of heart failure [J].
Chess, David J. ;
Stanley, William C. .
CARDIOVASCULAR RESEARCH, 2008, 79 (02) :269-278
[10]   Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction [J].
Cook, Stuart A. ;
Varela-Carver, Anabel ;
Mongillo, Marco ;
Kleinert, Christina ;
Khan, Muhammad T. ;
Leccisotti, Lucia ;
Strickland, Nicola ;
Matsui, Takashi ;
Das, Saumya ;
Rosenzweig, Anthony ;
Punjabi, Prakash ;
Camici, Paolo G. .
EUROPEAN HEART JOURNAL, 2010, 31 (01) :100-111