Sepsis is a dysregulated systemic response to infection and can lead to organ damage and death. Obesity is a significant problem worldwide and affects outcomes from sepsis. Our laboratory demonstrated that white adipose tissue (WAT) undergoes browning during sepsis, a process whereby WAT adopts a brown adipose tissue phenotype. However, this browning process was not observed in obese mice during sepsis. White adipose tissue browning is detrimental in patients with burn injury and cancer. We hypothesize that norepinephrine (NE) induces WAT browning in non-obese mice but not in obese mice similarly to sepsis-induced WAT browning. Six-week-old C57BL/6 male mice were randomized to a high-fat diet or normal diet. After 6-7 weeks of feeding, polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Norepinephrine was administered intraperitoneally via osmotic minipumps for 18h or 72h (no CLP) at which time tissue and plasma were harvested. Controls were mice that underwent CLP (no NE) with 18h harvest. A separate group of mice underwent pretreatment with NE or vehicle infusion for 72h, CLP was performed and at 18h had tissue and plasma harvested. Sepsis resulted in significant weight loss in both non-obese and obese mice. NE treatment alone caused weight loss in obese mice. Septic non-obese mice had higher UCP1 expression compared to control and obese septic mice. NE treatment increased UCP1 expression in non-obese, but not obese mice. NE treated obese septic mice had lower lung MPO activity, ALT, AST, TNFa and IL-6 levels compared to NE treated non-obese septic mice. Obesity protects mice from septic-induced and NE-induced WAT browning.

中文翻译：

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肥胖可防止脓毒症和去甲肾上腺素引起的白色脂肪组织褐变

脓毒症是对感染的一种失调的全身反应，可导致器官损伤和死亡。肥胖是世界范围内的一个重大问题，并影响败血症的结果。我们的实验室证明，白色脂肪组织 (WAT) 在败血症期间会发生褐变，这是 WAT 采用棕色脂肪组织表型的过程。然而，在败血症期间在肥胖小鼠中没有观察到这种褐变过程。白色脂肪组织褐变对烧伤和癌症患者是有害的。我们假设去甲肾上腺素 (NE) 在非肥胖小鼠中诱导 WAT 褐变，但在肥胖小鼠中与败血症诱导的 WAT 褐变类似。六周大的 C57BL/6 雄性小鼠被随机分配到高脂肪饮食组或正常饮食组。在喂食 6-7 周后，通过盲肠结扎和穿刺 (CLP) 诱导了多种微生物败血症。通过渗透性微型泵腹膜内施用去甲肾上腺素 18 小时或 72 小时（无 CLP），此时收集组织和血浆。对照是经过 18 小时收获的 CLP（无 NE）的小鼠。另一组小鼠接受 NE 或载体输注预处理 72 小时，进行 CLP，并在 18 小时收集组织和血浆。败血症导致非肥胖和肥胖小鼠的体重显着减轻。单独的NE治疗导致肥胖小鼠体重减轻。与对照和肥胖的脓毒症小鼠相比，脓毒症非肥胖小鼠具有更高的 UCP1 表达。NE 治疗增加了非肥胖小鼠的 UCP1 表达，但不增加肥胖小鼠。与 NE 治疗的非肥胖脓毒症小鼠相比，NE 治疗的肥胖脓毒症小鼠具有较低的肺 MPO 活性、ALT、AST、TNFa 和 IL-6 水平。肥胖保护小鼠免受脓毒症诱导和 NE 诱导的 WAT 褐变。