目的 探讨中脑星形胶质细胞源性神经营养因子（MANF）在小鼠白色脂肪(WAT)棕色化中的作用。方法 将成年野生型雄性小鼠分为两组，分别在室温与4℃的环境下饲养5 d，通过HE染色、免疫组织化学染色、Western blotting及Real-time PCR的方法确定WAT棕色化的模型构建成功后，检测MANF蛋白以及mRNA表达。采用局部注射腺相关病毒的方法，构建AAV-增强绿色荧光蛋白（EGFP）对照组和AAV-MANF实验组，通过免疫组织化学染色、Western blotting及Real-time PCR的方法检测酪氨酸羟化酶（TH）、产热基因以及线粒体相关基因的表达。结果 与室温饲养小鼠相比，冷刺激组小鼠腹股沟脂肪与附睾脂肪细胞体积变小，解耦联蛋白1（UCP1）免疫着色增强，UCP1蛋白及mRNA表达上调，产热基因及线粒体相关基因表达上调，TH蛋白表达上调，同时MANF蛋白与mRNA表达上调。在小鼠的腹股沟脂肪局部过表达MANF后，小鼠腹股沟脂肪细胞体积变小，UCP1阳性细胞增多，UCP1蛋白及mRNA表达上调，TH蛋白表达上调，产热基因以及线粒体基因表达也上调。结论 MANF表达上调与WAT棕色化密切相关，在小鼠的腹股沟脂肪过表达MANF可以促进WAT发生棕色化。

Objective To investigate the role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in the browning of white adipose tissue in mice. Methods Adult male wild-type mice were divided into two groups and housed at room temperature or 4°C for 5 days, respectively. After confirming the successful establishment of the white adipose tissue (WAT） browning model using HE staining, immunohistochemical staining, Western blotting, and Real-time PCR, the expression levels of MANF were detected at both protein and mRNA levels. Adeno-associated virus (AAV)-mediated local injection was used to establish the control group (AAV-EGFP) and the experimental group (AAV-MANF). The expression levels of tyrosine hydroxylase (TH), thermogenic genes, and mitochondrial-related genes were detected by immunohistochemical staining, Western blotting, and Real-time PCR. Results Compared with mice housed at room temperature, mice in the cold stimulation group showed smaller cell sizes in inguinal adipose tissue and epididymal adipose tissue，enhanced uncoupling protein 1 (UCP1) immunostaining，upregulated UCP1 expression at both protein and mRNA levels, increased expression of thermogenic genes and mitochondrial-related genes, elevated TH protein level, as well as upregulated MANF expression at both protein and mRNA levels. After local overexpression of MANF in inguinal adipose tissue of mice, the inguinal adipocyte size was reduced, the number of UCP1-positive cells was increased, the expression of UCP1 was upregulated at both protein and mRNA levels, the TH protein level was elevated, and the expression of thermogenic genes and mitochondrial genes was also increased. Conclusion The upregulation of MANF expression is closely associated with WAT browning, and local overexpression of MANF in inguinal adipose tissue of mice can promote the browning of WAT.