Reduced body weight in male Tspan8-deficient mice
Reduced body weight in male Tspan8-deficient mice
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DOI：
10.1038/ijo.2010.165
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发表时间：
2011-04-01
影响因子：
4.9
通讯作者：
Blom, D.
中科院分区：
文献类型：
--
作者：
Champy, M-F;Le Voci, L.;Blom, D.
目的：基因TSPAN8最近在一项全基因组关联研究中被确定为北欧个体中与2型糖尿病（T2D）风险相关的基因座中最可能的致病基因。为了评估Tspan8是否是该基因座中真正的t2d致病基因，我们在小鼠中切除了其表达，并确定了这种切除对多种代谢性状的影响。结果：我们发现，小鼠中Tspan8的基因消融导致喂食正常食物的雄性小鼠体重减少（-15.6%），这种缺乏导致喂食高脂肪和高碳水化合物饮食时对体重增加（-13.7%）的抵抗力。体重的差异只能在雄性小鼠中检测到，并且是脂肪沉积减少和瘦体重减少的结果（分别为16.9%和11%）。尽管体重有显著差异，但在Tspan8基因敲除小鼠中，空腹胰岛素和葡萄糖水平没有变化，在口服葡萄糖耐量试验和腹腔胰岛素敏感性试验研究中，我们也没有分别发现葡萄糖清除率和胰岛素敏感性的变化。此外，雄性Tspan8基因敲除小鼠的骨密度和磷水平显著降低（分别为6.2和16.6%）。Tspan8在小鼠的消化组织中表达最高，而在胰腺中几乎不表达。相比之下，人类TSPAN8在消化组织和胰腺细胞中大量表达。结论：我们的研究结果证明了Tspan8在男性体重调节中的作用，但并没有显示出先前人类全基因组关联研究中预期的t2d相关性状的差异。小鼠和人体组织中Tspan8表达水平的差异表明，Tspan8在这些生物体中可能具有不同或额外的生理功能。国际肥胖杂志（2011）35,605-617；doi: 10.1038 / ijo.2010.165;2010年8月24日在线发布
Objective: The gene TSPAN8 was recently identified in a genome-wide association study as the most likely causal gene in a locus that was correlated with the risk of type 2 diabetes (T2D) in northern European individuals. To assess whether Tspan8 is the actual T2D-causal gene in this locus, we ablated its expression in mice and determined the consequences of this ablation on a multitude of metabolic traits.Results: We found that genetic ablation of Tspan8 in mice results in a reduction (-15.6%) in the body weight of males fed a normal chow diet and that this deficiency results in a resistance to body weight gain (-13.7%) upon feeding a high fat and high carbohydrate diet. The differences in body weight could only be detected in male mice and were the consequence of both a decrease in fat deposition, and a decrease in lean body mass (16.9 and 11%, respectively). In spite of the significant body weight difference, no changes in fasting insulin and glucose levels could be detected in Tspan8 knockout mice, nor could we identify changes in the clearance of glucose or sensitivity to insulin in oral glucose tolerance test and intraperitoneal insulin sensitivity test studies, respectively. In addition, male Tspan8 knockout mice showed significantly lower bone mineral density and phosphorus levels (6.2 and 16.6%, respectively). Expression of Tspan8 in mouse was highest in digestive tissues, but virtually absent from the pancreas. In contrast, expression of human TSPAN8 was substantial in digestive tissues, as well as pancreatic cells.Conclusions: Our results argue for a role for Tspan8 in body-weight regulation in males, but do not show differences in T2D-associated traits that were anticipated from previous human genome-wide association studies. Differences in Tspan8 expression levels in mouse and human tissues suggest that Tspan8 could fulfill different or additional physiological functions in these organisms. International Journal of Obesity (2011) 35, 605-617; doi: 10.1038/ijo.2010.165; published online 24 August 2010