Sarvas Jessica L, Niccoli Sarah, Walser Eric, Khaper Neelam, Lees Simon J
Medical Sciences Division, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.
Medical Sciences Division, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada.
Physiol Rep. 2014 Jul 4;2(7). doi: 10.14814/phy2.12064. Print 2014 Jul 1.
This study was designed to investigate the role of interleukin-6 (IL-6) on high-fat diet (HFD)-induced glucose intolerance, and the response to voluntary physical activity in the prevention of insulin resistance. Six-week-old wild-type (WT) and IL-6 knockout (KO) mice with (RUN) or without (SED) access to running wheels were fed a HFD (60% from kcal) for 4 weeks. A glucose tolerance test revealed that blood glucose levels were 25-30% higher in KO RUN compared to all other groups. In WT RUN, weight gain was positively correlated with total caloric intake; however, this correlation was absent in KO RUN. In soleus muscle, there was a 2-fold increase in SOCS3 expression in KO RUN compared to all other groups. In gastrocnemius and plantaris muscles, Akt phosphorylation was 31% higher in WT RUN compared to WT SED, but this effect of running was absent in KO mice. Additionally, there was a 2.4-fold increase in leptin expression in KO RUN compared to KO SED in the gastrocnemius and plantaris muscles. In the liver, there was a 2- to 3.8-fold increase in SOCS3 expression in KO SED compared to all other groups, and AMPKα phosphorylation was 27% higher in WT mice (both RUN and SED) compared to KO mice (both RUN and SED). This study provides new insights into the role of the IL-6 in metabolism and energy storage, and highlights tissue-specific changes in early signaling pathways in response to HFD for 4 weeks. The collective findings suggest that endogenous IL-6 is important for the prevention of insulin resistance leading to type 2 diabetes.
本研究旨在探讨白细胞介素-6（IL-6）在高脂饮食（HFD）诱导的葡萄糖不耐受中的作用，以及在预防胰岛素抵抗方面对自愿性体育活动的反应。六周龄的野生型（WT）和IL-6基因敲除（KO）小鼠，分为可使用（RUN）或不使用（SED）跑步轮的两组，给予高脂饮食（热量的60%）持续4周。葡萄糖耐量试验显示，与所有其他组相比，KO RUN组的血糖水平高25%-30%。在WT RUN组中，体重增加与总热量摄入呈正相关；然而，KO RUN组不存在这种相关性。在比目鱼肌中，与所有其他组相比，KO RUN组中SOCS3表达增加了2倍。在腓肠肌和跖肌中，WT RUN组的Akt磷酸化水平比WT SED组高31%，但跑步对KO小鼠没有这种作用。此外，与KO SED组相比，KO RUN组在腓肠肌和跖肌中的瘦素表达增加了2.4倍。在肝脏中，与所有其他组相比，KO SED组的SOCS3表达增加了2至3.8倍，WT小鼠（RUN和SED组）的AMPKα磷酸化水平比KO小鼠（RUN和SED组）高27%。本研究为IL-6在代谢和能量储存中的作用提供了新的见解，并突出了在高脂饮食4周后早期信号通路中的组织特异性变化。这些研究结果共同表明，内源性IL-6对预防导致2型糖尿病的胰岛素抵抗很重要。
