Gong Maolei, Liu Chuanguo, Zhang Liang, Zhang Hongbin, Pan Jie
Shandong Provincial Key Laboratory of Animal Resistant Biology, College of Life Sciences, Shandong Normal University, #88 East Wenhua Ave., Jinan, 250014, People's Republic of China.
Mol Cell Biochem. 2014 Jun;391(1-2):59-66. doi: 10.1007/s11010-014-1987-5. Epub 2014 Feb 13.
Tumor necrosis factor alpha (TNFα) is an adipokine involved in the regulation of cell differentiation and lipid metabolism, but its specific role has not been clearly understood. We validated a hypothesis that loss of TNFα function would inhibit Wnt/β-catenin signaling and accelerate adipogenesis in adolescent genetic obese mice. Epididymal white adipose tissues (eWAT) from TNFα deficient (TNFα(-/-)), leptin receptor deficient (db/db) and double gene mutant (db/db/TNFα(-/-), DT) male mice were used for comparative analysis of key molecules in Wnt/β-catenin signaling and adipogenic markers by qRT-PCR and western blot techniques. Compared with TNFα(-/-) and WT mice of 28 days old, an obese trait was observed in both db/db and DT mice, while the latter showed more significant body weight gain and eWAT hypertrophy. The mRNA level of key molecules in Wnt/β-catenin pathway was reduced in both obese groups, while the DT group was the lowest. Expression of adipocyte-specific genes was up-regulated during obese development in the two obese groups, while the DT group revealed more correlation than that of db/db group. At the protein level, a down regulation of Wnt10b and β-catenin in obese eWAT showed similar tendency with that of mRNA level. Compared with the lean groups, the levels of adiponectin and PPARγ2 for the obese groups were down-regulated at 21-day-old age, while they were elevated at older age. Our results suggested that deficiency in TNFα inhibited Wnt/β-catenin signaling of the obese eWAT and up-regulated expression of adipokines, and accelerated adipogenesis in genetic obese mice on a chow diet.
肿瘤坏死因子α（TNFα）是一种参与细胞分化和脂质代谢调节的脂肪因子，但其具体作用尚未完全明确。我们验证了一个假设，即TNFα功能丧失会抑制Wnt/β-连环蛋白信号通路，并加速青春期遗传性肥胖小鼠的脂肪生成。通过qRT-PCR和蛋白质印迹技术，对来自TNFα缺陷（TNFα(-/-)）、瘦素受体缺陷（db/db）和双基因突变（db/db/TNFα(-/-)，DT）雄性小鼠的附睾白色脂肪组织（eWAT）进行Wnt/β-连环蛋白信号通路关键分子和成脂标志物的比较分析。与28日龄的TNFα(-/-)和野生型小鼠相比，db/db和DT小鼠均出现肥胖特征，而DT小鼠体重增加和eWAT肥大更为显著。两个肥胖组中Wnt/β-连环蛋白通路关键分子的mRNA水平均降低，而DT组最低。两个肥胖组在肥胖发展过程中脂肪细胞特异性基因的表达上调，而DT组的相关性高于db/db组。在蛋白质水平上，肥胖eWAT中Wnt10b和β-连环蛋白的下调与mRNA水平表现出相似的趋势。与瘦组相比，肥胖组脂联素和PPARγ2水平在21日龄时下调，而在老年时升高。我们的结果表明，TNFα缺乏抑制了肥胖eWAT的Wnt/β-连环蛋白信号通路，上调了脂肪因子的表达，并加速了正常饮食的遗传性肥胖小鼠的脂肪生成。
