Wntless基因抑制棕色脂肪组织发育和能量代谢  

Wntless represses brown adipose tissue differentiation and energy expenditure

作　　者：曹怡玮 张伟[1] 刘培 郭熙志[1] Cao Yiwei;Zhang Wei;Liu Pei;Guo Xizhi(Bio-X Institutes,Shanghai Jiao Tong University,Shanghai 200240,China)

机构地区：[1]上海交通大学Bio-X研究中心,200240

出　　处：《中华内分泌代谢杂志》2019年第4期323-329,共7页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金项目(31271553).

摘　　要：目的研究Wntless (Wls)介导的Wnt信号通路对棕色脂肪组织(BAT)发育分化及能量代谢的影响。方法运用Cre-loxP系统,在Myf5^+的棕色脂肪前体细胞敲除Wls基因。取敲除小鼠WlsMyf5^Δ/Δ和Wls^fl/fl对照小鼠的BAT进行形态观察、免疫组化分析、实时定量PCR以及Western印迹检测,观察其细胞分化状态;取BAT的血管基质部分(SVF)细胞进行体外棕色化诱导、油红O染色、实时定量PCR和细胞呼吸实验,分析细胞体外分化潜能和氧耗水平;对小鼠进行红外热成像,测定肛温以及氧耗呼吸代谢,分析小鼠产热和能量代谢状态;对小鼠进行核磁共振体脂检测,葡萄糖和胰岛素耐量试验,检测小鼠脂肪含量和糖代谢能力。结果Wls基因敲除小鼠体型偏小,体重偏轻,瘦脂比升高,棕色脂肪组织体积较小,背部体温升高;敲除小鼠BAT的分化增强,产热增加,解耦联蛋白1(Ucp1)的mRNA和蛋白表达水平上升,其SVF细胞体外棕色化明显增强;敲除小鼠体脂量下降,糖代谢能力升高,但整体氧耗呼吸能量代谢没有明显变化。结论Wls介导的Wnt信号通路能通过抑制小鼠棕色脂肪组织分化,降低其产热和葡萄糖代谢。Objective To explore the effect of Wntless (Wls)-mediated Wnt signaling on the development and energy metabolism of brown adipose tissue (BAT). Methods BAT-specific Wls knockout (WlsMyf5^Δ/Δ) mice were generated by Cre-loxP system. The differentiations of BAT in WlsMyf5^Δ/Δ knockout mice and Wls^fl/fl control mice were analyzed by histological morphology, immunohistochemistry, real-time PCR, and Western blot. After stromal vascular fraction (SVF) cells in BAT were induced to differentiate, oil red O staining, real-time PCR, and cell respiration experiments were performed for analyzing in-vitro cell differentiation and oxygen consumption. The energy metabolism of mice was monitored by rectal temperature, oxygen consumption rate in BAT, and energy expenditure. The adiposity of mice was evaluated by NMR while the glucose metabolism was analyzed by the glucose and insulin tolerance tests. Results The WlsMyf5^Δ/Δ knockout mice appeared smaller body size, lower weight, higher percentage of lean fat, lower size of BAT, with higher body temperature on the back as compared to Wls^fl/fl control mice. The differentiation and thermogenesis of BAT in Wls-deficient mice were relatively augmented, along with an increase in Ucp1 mRNA and protein expressions. SVF cells from BAT in WlsMyf5^Δ/Δ knockout mice revealed enhanced brown differentiation. Adiposity was decreased and glucose metabolic capacity was enhanced in the WlsMyf5^Δ/Δ knockout mice, without significant change in oxygen consumption of the whole body. Conclusion Wls-mediated Wnt signaling decreases the thermogenesis and glucose metabolism of BAT by suppressing its differentiation.

关 键 词：WNT信号通路 Wntless基因 棕色脂肪组织 

分 类 号：R589.2[医药卫生—内分泌]