Anunciado-Koza Rea P, Higgins David C, Koza Robert A
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
Biochimie. 2016 May;124:134-140. doi: 10.1016/j.biochi.2015.05.007. Epub 2015 May 21.
The expression of a subset of genes including mesoderm specific transcript (Mest), secreted frizzled-related protein 5 (Sfrp5) and bone morphogenetic protein 3 (Bmp3) in adipose tissue biopsies of C57BL/6J mice before exposure to an obesogenic diet were shown to be predictive for the development of obesity in mice after feeding a high fat diet for 8 weeks. This observation led to the supposition that adipose tissue expression of this subset of genes within inbred strains of mice could be associated with their susceptibility in the development of adiposity when fed a low fat diet. The analyses of male mice from 5 inbred strains showed average bodyweights ranging from 25.82 to 36.58 g at 16 weeks of age. Bodyweight was highest for AKR/J and adiposity correlated highly with bodyweight for all strains. Analyses of epididymal fat gene expression showed Mest, Sfrp5 and Bmp3 to be highly concomitant with adiposity across all strains of mice. Naked 1 (Nkd1), a gene previously shown to be associated with variations of adiposity in mice fed a high fat diet, but not predictive for the development of adiposity, showed no correlation with adiposity. In addition, the expression of Mest and Sfrp5 were tightly associated across the 5 mouse strains with the highest and lowest expression occurring in DBA/2J and C57BL/6J (B6) respectively suggesting a common mechanism for their regulation. Surprisingly, when independent cohorts for these 2 strains were fed high fat diet for 8 weeks, DBA/2J showed no further increase in Sfrp5 expression whereas expression levels for B6 mice were induced almost 20-fold. Analyses of (B6 x DBA2/J) F1 mice fed a low fat diet for 8 weeks showed intermediate levels of adiposity and gene expression for Sfrp5 and Mest suggesting a strong genetic basis for these differences.
在C57BL/6J小鼠暴露于致肥胖饮食之前,其脂肪组织活检中包括中胚层特异性转录物(Mest)、分泌型卷曲相关蛋白5(Sfrp5)和骨形态发生蛋白3(Bmp3)在内的一组基因的表达,被证明可预测小鼠在高脂饮食喂养8周后肥胖的发生。这一观察结果导致推测,在近交系小鼠中,该组基因在脂肪组织中的表达可能与其在低脂饮食喂养时肥胖发生的易感性有关。对来自5个近交系的雄性小鼠的分析表明,16周龄时平均体重在25.82至36.58克之间。AKR/J的体重最高,所有品系的肥胖程度与体重高度相关。附睾脂肪基因表达分析表明,在所有品系的小鼠中,Mest、Sfrp5和Bmp3与肥胖高度相关。Naked 1(Nkd1)是一个先前已证明与高脂饮食喂养小鼠的肥胖变化相关,但不能预测肥胖发生的基因,它与肥胖无相关性。此外,在这5个小鼠品系中,Mest和Sfrp5的表达紧密相关,最高和最低表达分别出现在DBA/2J和C57BL/6J(B6)中,这表明它们的调控存在共同机制。令人惊讶的是,当这两个品系的独立队列喂养高脂饮食8周时,DBA/2J的Sfrp5表达没有进一步增加,而B6小鼠的表达水平几乎诱导了20倍。对喂食低脂饮食8周的(B6×DBA2/J)F1小鼠的分析表明,Sfrp5和Mest的肥胖程度和基因表达水平处于中间,这表明这些差异有很强的遗传基础。