Division of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 2005, Cincinnati, OH 45229, USA.
Biochim Biophys Acta Mol Basis Dis. 2017 Oct;1863(10 Pt B):2654-2660. doi: 10.1016/j.bbadis.2017.06.008. Epub 2017 Jun 15.
Little is known about how obesity affects the heart during sepsis and we sought to investigate the obesity-induced cardiac effects that occur during polymicrobial sepsis. Six-week old C57BL/6 mice were randomized to a high fat (HFD) (60% kcal fat) or normal diet (ND) (16% kcal fat). After 6weeks of feeding, mice were anesthetized with isoflurane and polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Plasma and cardiac tissue were obtained for analysis. Echocardiography was performed on a separate cohort of mice at 0 and 18h after CLP. Following 6-weeks of dietary intervention, plasma cardiac troponin I was elevated in obese mice at baseline compared to non-obese mice but troponin increased only in non-obese septic mice. IL-17a expression was 27-fold higher in obese septic mice versus non-obese septic mice. Cardiac phosphorylation of STAT3 at Ser727 was increased at baseline in obese mice and increased further only in obese septic mice. Phosphorylation of STAT3 at Tyr705 was similar in both groups at baseline and increased after sepsis. SOCS3, a downstream protein and negative regulator of STAT3, was elevated in obese mice at baseline compared to non-obese mice. After sepsis non-obese mice had an increase in SOCS3 expression that was not observed in obese mice. Taken together, we show that obesity affects cardiac function and leads to cardiac injury. Furthermore, myocardial injury in obese mice during sepsis may occur through alteration of the STAT3 pathway.
关于肥胖如何在脓毒症期间影响心脏，我们知之甚少，因此我们试图研究多微生物脓毒症期间发生的肥胖引起的心脏效应。将 6 周龄 C57BL/6 小鼠随机分为高脂肪（HFD）（60%卡路里脂肪）或正常饮食（ND）（16%卡路里脂肪）组。喂养 6 周后，用异氟烷麻醉小鼠，并通过盲肠结扎和穿刺（CLP）诱导多微生物脓毒症。采集血浆和心脏组织进行分析。在 CLP 后 0 和 18 小时，对另一组小鼠进行超声心动图检查。经过 6 周的饮食干预，肥胖小鼠的血浆心肌肌钙蛋白 I 在基线时高于非肥胖小鼠，但仅在非肥胖脓毒症小鼠中升高。肥胖脓毒症小鼠的 IL-17a 表达比非肥胖脓毒症小鼠高 27 倍。肥胖小鼠的心脏 STAT3 丝氨酸 727 磷酸化在基线时增加，仅在肥胖脓毒症小鼠中进一步增加。STAT3 的酪氨酸 705 磷酸化在两组中的基线时相似，并在脓毒症后增加。SOCS3 是 STAT3 的下游蛋白和负调节剂，肥胖小鼠的 SOCS3 表达在基线时高于非肥胖小鼠。在脓毒症后，非肥胖小鼠的 SOCS3 表达增加，但肥胖小鼠没有观察到这种增加。总之，我们表明肥胖会影响心脏功能并导致心脏损伤。此外，肥胖小鼠在脓毒症期间的心肌损伤可能是通过改变 STAT3 途径发生的。
