Gene-by-diet interactions influence calcium absorption and bone density in mice.
Gene-by-diet interactions influence calcium absorption and bone density in mice.
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DOI：
10.1002/jbmr.2065
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发表时间：
2014-03
影响因子：
6.2
通讯作者：
Fleet, James C.
中科院分区：
文献类型：
--
作者：
Replogle, Rebecca A.;Li, Qiang;Wang, Libo;Zhang, Min;Fleet, James C.
膳食钙（Ca）的摄入量需要达到峰值骨矿物质密度（BMD）。习惯性低钙摄入可提高肠道钙吸收效率，保护骨量，但这种适应性反应的控制机制以及遗传对其的影响尚不清楚。从4-12周龄开始，我们给11个遗传多样的自交系小鼠饲喂正常（0.5%）或低（0.25%）钙的饲粮（每系8只），研究了饲粮和遗传对钙和骨代谢的独立和相互作用影响。在包括钙吸收在内的所有骨骼、肾脏和肠道表型中观察到显著的遗传变异。不同品系对低钙饲料的钙吸收和骨参数的适应也存在显著差异。Ca吸收与股骨BMD （r=0.17, p=0.02）、股骨远端BV/TV （r=0.34, p<0.0001）呈正相关。虽然钙吸收与1,25二羟基维生素D （1,25(OH)2D）相关（r=0.35， P<0.0001），但在11个品系中，钙吸收对低钙摄入的适应与饮食诱导的1,25(OH)2D适应无关。一些肠道蛋白被提出介导钙的吸收；claudin 2和12，电压门控钙通道v1.3 (Cav1.3)，质膜钙atp酶1b (PMCA1b)，瞬时受体电位香草酸苷成员6 （TRPV6）和钙结合蛋白D9k （CaBPD9k）。只有TRPV6、CaBPD9k和PMCA1b的mRNA水平与Ca吸收有关（r分别为0.42、0.43和0.21）。然而，目前的模型无法解释钙吸收的大量变化，这表明新的机制仍有待确定。这些观察结果为以发现为重点的倡议奠定了基础，以确定控制基因-饮食相互作用影响钙/骨代谢的新遗传因素。
Dietary calcium (Ca) intake is needed to attain peak bone mineral density (BMD). Habitual low Ca intake increases intestinal Ca absorption efficiency to protect bone mass but the mechanism controlling, and the impact of genetics on, this adaptive response is not clear. We fed 11 genetically diverse inbred mouse lines a normal (0.5%) or low (0.25%) Ca diet from 4-12 wks of age (n=8 per diet per line) and studied the independent and interacting effects of diet and genetics on Ca and bone metabolism. Significant genetic variation was observed in all bone, renal, and intestinal phenotypes measured including Ca absorption. Also, adaptation of Ca absorption and bone parameters to low dietary Ca was significantly different among the lines. Ca absorption was positively correlated to femur BMD (r=0.17, p=0.02), and distal femur BV/TV (r=0.34, p<0.0001). While Ca absorption was correlated to 1,25 dihydroxyvitamin D (1,25(OH)2D) (r=0.35, P<0.0001), the adaptation of Ca absorption to low Ca intake did not correlate to diet-induced adaptation of 1,25(OH)2D across the 11 lines. Several intestinal proteins have been proposed to mediate Ca absorption; claudins 2 and 12, voltage gated Ca channel v1.3 (Cav1.3), plasma membrane Ca ATPase 1b (PMCA1b), transient receptor potential vanilloid member 6 (TRPV6) and calbindin D9k (CaBPD9k). Only the mRNA levels for TRPV6, CaBPD9k, and PMCA1b were related to Ca absorption (r= 0.42, 0.43, and 0.21, respectively). However, a significant amount of the variation in Ca absorption is not explained by the current model and suggests that novel mechanisms remain to be determined. These observations lay the groundwork for discovery-focused initiatives to identify novel genetic factors controlling gene-by-diet interactions affecting Ca/bone metabolism.
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影响因子：
5.3
作者：
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影响因子：
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