Sweet taste receptor deficient mice have decreased adiposity and increased bone mass.

Sweet taste receptor deficient mice have decreased adiposity and increased bone mass.
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DOI:
10.1371/journal.pone.0086454
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
MacDougald OA
MacDougald OA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Simon BR;Learman BS;Parlee SD;Scheller EL;Mori H;Cawthorn WP;Ning X;Krishnan V;Ma YL;Tyrberg B;MacDougald OA

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甜味受体(T1R2和T1R3)的功能表达在许多代谢组织中都有报道,包括肠道、胰腺,最近在脂肪组织中也有表达。有研究表明,这些非味觉组织中的甜味受体可能在全身能量平衡和代谢中发挥作用。据报道,在高碳水化合物饮食的T1R3基因敲除小鼠中,脂肪储备较小,甜味受体在体外调节脂肪生成。为了评估甜味受体对脂肪组织生物学的潜在贡献,我们研究了T1R2和T1R3基因敲除小鼠的脂肪组织表型。在这里,我们提供数据来证明,当喂养肥胖饮食时,T1R2和T1R3基因敲除小鼠都减少了肥胖和较小的脂肪细胞。虽然在T1R3缺乏症中观察到轻度糖耐量异常,但分析的其他代谢变量在不同的基因型间是相似的。此外,T1R2基因敲除小鼠的进食量、呼吸商、耗氧量和体力活动没有变化。虽然T1R2缺乏对外周脂肪储备中的脂肪细胞数量没有影响,但在这些基因敲除的动物中,骨髓脂肪细胞的数量显著减少。最后,我们提供的数据表明,T1R2和T1R3基因敲除小鼠的皮质骨量和骨小梁重塑增加。本报告鉴定了甜味受体在脂肪和骨生物学调节中的新功能,并认为在这些背景下,T1R2和T1R3的活动要么相互依赖,要么在体内具有共同的独立作用。
Functional expression of sweet taste receptors (T1R2 and T1R3) has been reported in numerous metabolic tissues, including the gut, pancreas, and, more recently, in adipose tissue. It has been suggested that sweet taste receptors in these non-gustatory tissues may play a role in systemic energy balance and metabolism. Smaller adipose depots have been reported in T1R3 knockout mice on a high carbohydrate diet, and sweet taste receptors have been reported to regulate adipogenesis in vitro. To assess the potential contribution of sweet taste receptors to adipose tissue biology, we investigated the adipose tissue phenotypes of T1R2 and T1R3 knockout mice. Here we provide data to demonstrate that when fed an obesogenic diet, both T1R2 and T1R3 knockout mice have reduced adiposity and smaller adipocytes. Although a mild glucose intolerance was observed with T1R3 deficiency, other metabolic variables analyzed were similar between genotypes. In addition, food intake, respiratory quotient, oxygen consumption, and physical activity were unchanged in T1R2 knockout mice. Although T1R2 deficiency did not affect adipocyte number in peripheral adipose depots, the number of bone marrow adipocytes is significantly reduced in these knockout animals. Finally, we present data demonstrating that T1R2 and T1R3 knockout mice have increased cortical bone mass and trabecular remodeling. This report identifies novel functions for sweet taste receptors in the regulation of adipose and bone biology, and suggests that in these contexts, T1R2 and T1R3 are either dependent on each other for activity or have common independent effects in vivo.
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