State Key laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular research Institute, Wuhan University, Wuhan 430060, China; Hubei key Laboratory of Cardiology, Wuhan 430060, China.
Biochim Biophys Acta Mol Basis Dis. 2017 Dec;1863(12):3128-3141. doi: 10.1016/j.bbadis.2017.08.022. Epub 2017 Aug 24.
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.
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.
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.
Our results suggest that IL-6 contributes to limit lipid metabolic disorder, cardiac hypertrophy, fibrosis, inflammation and myocardium lipotoxicity during HFD-induced obesity.
肥胖与代谢紊乱和慢性炎症有关，后者在心血管疾病中起着关键作用。IL-6 参与调节与肥胖相关的脂质代谢和炎症。在本研究中，我们试图确定 IL-6 在高脂肪饮食（HFD）诱导的心肌病中的作用，并探讨其信号通路。
雌性，5 周龄的 IL-6 敲除（KO）和同窝小鼠分别喂食正常饮食（ND，10%脂肪）或 HFD（45%脂肪）14 周。治疗结束时，通过超声心动图评估心功能。收集脂肪组织和血浆进行进一步测量。用 CD68 免疫组化检测心脏炎症。进行 Masson 三色染色和油红 O 染色评估心脏纤维化和脂质积聚。对心脏组织进行实时 PCR 和 Western 免疫印迹分析以探讨潜在机制。
IL-6 KO 小鼠在基线时与 WT 小鼠相比表现出胰岛素抵抗增加。当喂食 HFD 时，与喂食 ND 的 IL-6 KO 小鼠相比，IL-6 KO 小鼠的体重和脂肪量增加减少，胰岛素抵抗增加。此外，IL-6 KO 小鼠在 HFD 诱导的肥胖期间出现心脏功能障碍。组织学分析表明，在 HFD 处理期间，IL-6 KO 小鼠的心脏中脂质积聚、纤维化和炎症增加，但不影响心脏形态。最后，在 HFD 诱导的肥胖期间，IL-6 缺乏增加了心脏中 AMPK 和 ACC 的磷酸化。
我们的结果表明，IL-6 有助于限制 HFD 诱导的肥胖期间的脂质代谢紊乱、心脏肥大、纤维化、炎症和心肌脂毒性。
