MSR1 increases the thermogenic capacity of adipose tissue by promoting the polarization of M2 macrophages
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摘要:
目的：探讨A1类清道夫受体（macrophage scavenger receptor 1，MSR1）在低温刺激诱导白色脂肪产热进程中的作用及其机制。方法：正常饮食（common diet，CD）的野生型小鼠（MSR1+/+）和MSR1缺失表达小鼠（MSR1-/-）分别给予低温刺激1 d 或者 14 d 后，通过 qRT-PCR、Western blot 和免疫组织化学染色检测皮下白色脂肪组织（subcutaneous white adipose tissue， scWAT）和棕色脂肪组织（brown adipose tissue，BAT）中脂肪产热能力标志物（UCP1、Cidea和Cox8b）的表达。qRT-PCR和流式细胞术检测正常饮食的MSR1+/+和MSR1-/-小鼠给予低温刺激14 d后，小鼠scWAT中巨噬细胞极化情况。建立高脂饮食（high fat diet，HFD）诱导的小鼠肥胖模型，监测CD和HFD 12周的MSR1+/+和MSR1-/-小鼠体重变化，并使用代谢笼监测小鼠耗氧量和产热量变化；qRT-PCR和免疫组织化学染色检测HFD 12周的小鼠给予低温刺激7 d后，小鼠scWAT和BAT中产热基因表达。 体外实验应用巨噬细胞条件培养基刺激小鼠前脂肪细胞分化，待分化成熟后应用qRT-PCR检测产热基因表达。结果：慢性低温刺激下，与MSR1+/+小鼠相比，MSR1-/-小鼠脂肪组织产热基因表达明显降低。进一步，MSR1-/-小鼠scWAT中M2型巨噬细胞数量明显减少。HFD喂养12周后，MSR1-/-小鼠体重增加更为明显，并且耗氧量和产热量明显降低。低温刺激下，与MSR1+/+ HFD小鼠相比，MSR1-/- HFD小鼠脂肪产热能力明显降低。体外细胞研究发现，与MSR1+/+小鼠腹腔巨噬细胞条件培养基诱导的成熟脂肪细胞相比，MSR1-/-小鼠腹腔巨噬细胞条件培养基诱导的成熟脂肪细胞产热基因表达明显降低。结论：低温刺激下，MSR1通过增加M2型巨噬细胞极化促进小鼠脂肪组织产热。
Abstract:
Objective：This study aims to investigate the role and mechanism of macrophage scavenger receptor 1（MSR1）in the process of white adipose thermogenesis induced by cold exposure. Methods：The expression of MSR1 and markers of the thermogenic capacity of adipose（UCP1，Cidea，Cox8b）in subcutaneous white adipose tissue（scWAT）and brown adipose tissue（BAT）of wild type mice（MSR1 +/+）and MSR1 knockout mice（MSR1-/-）fed with common diet（CD）were detected by qRT - PCR，Western blot and immunohistochemistry after 1 or 14 days of cold exposure. The polarization of macrophages in scWAT of MSR1+/+ and MSR1-/- mice fed with CD after 30 days of cold exposure were detected by qRT-PCR and flow cytometry. Obese mouse model was established by high fat diet（HFD），the weight changes were monitored in MSR1+/+ and MSR1-/- mice fed with CD or HFD for 12 weeks，and the metabolic cage method was used to monitor the changes of O2 consumption and heat production. The expression of thermogenic genes in scWAT and BAT of mice fed with HFD for 12 weeks were detected by qRT-PCR and immunohistochemistry after 7 days of cold exposure. In vitro， macrophage conditioned medium was used to stimulate the differentiation of mouse preadipocytes，and the expression of thermogenic genes of mature adipocytes were detected by qRT-PCR. Results：Compared with MSR1+/+ mice，the expression of thermogenic genes in adipose tissue of MSR1-/- mice was significantly decreased. Further，the number of M2 macrophages in scWAT of MSR1-/- mice decreased significantly. After fed with HFD for 12 weeks，MSR1-/- mice had significantly higher weight，lower O2 consumption and heat production. The thermogenic capacity of adipose tissue in MSR1-/- HFD mice was significantly reduced compared with MSR1 +/+ HFD mice after cold exposure. In vitro cell studies，compared with the mature adipocytes induced by peritoneal macrophage conditioned medium in MSR1 +/+ mice，the expression of thermogenic genes in mature adipocytes induced by peritoneal macrophage conditioned medium in MSR1-/- mice was significantly reduced. Conclusion：After cold exposure，MSR1 increases the thermogenic capacity of adipose tissue by promoting the polarization of M2 macrophages.
