Effects of Combined Exposure to Lead and High-Fat Diet on Bone Quality in Juvenile Male Mice.
Effects of Combined Exposure to Lead and High-Fat Diet on Bone Quality in Juvenile Male Mice.
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DOI：
10.1289/ehp.1408581
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发表时间：
2015-10
影响因子：
10.4
通讯作者：
Mooney RA
中科院分区：
文献类型：
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作者：
Beier EE;Inzana JA;Sheu TJ;Shu L;Puzas JE;Mooney RA
铅暴露和肥胖是年轻人骨量减少的共同危险因素，特别是在社会经济水平较低的社区。这项研究的目的是确定铅暴露和高脂饮食诱导的肥胖的并存是否会放大与这些危险因素中的每一个独立相关的骨骼缺陷，并探索观察到的缺陷的相关机制。将5周龄雄性C57BL/6J小鼠分别给予低脂(10%大卡，LFD)和高脂(60%大卡，HFD)饲料喂养12周。小鼠通过饮水暴露于终生铅(50ppm)。HFD与体重增加和糖耐量减低有关。高脂饲料和铅均可提高空腹血糖和血清瘦素水平。PB和HFD都降低了骨小梁质量，共同对这些骨参数产生了进一步的不利影响。铅暴露对骨的力学性能有一定的抑制作用，而高脂饲料对其无明显影响。铅和HFD都改变了祖细胞的分化，促进了破骨细胞的生成，增加了脂肪的生成，同时抑制了成骨细胞的生成。通过改变Wnt信号来支持这一谱系转变，铅和MC3T3细胞中的非酯化脂肪酸在体外增加了PPAR-γ的活性，抑制了β-连接素的活性。铅和非酯化脂肪酸的结合增强了这些效应。PB和HFD在骨积累方面产生了选择性缺陷，这与祖细胞活动的改变有关，这可能涉及Wnt信号的减少。这项研究强调需要评估毒物以及与人类健康和疾病相关的其他风险因素。贝尔·EE，英扎娜·贾，舒天杰，舒·L，普扎斯·耶，穆尼·拉斐尔。2015年。铅和高脂饮食联合暴露对幼年雄性小鼠骨质量的影响。环境健康展望123:935–943； http://dx.doi.org/10.1289/ehp.1408581
Lead (Pb) exposure and obesity are co-occurring risk factors for decreased bone mass in the young, particularly in low socioeconomic communities. The goal of this study was to determine whether the comorbidities of Pb exposure and high-fat diet–induced obesity amplify skeletal deficits independently associated with each of these risk factors, and to explore associated mechanisms of the observed deficiencies. Five-week-old male C57BL/6J mice were placed on low-fat (10% kcal, LFD) or high-fat (60% kcal, HFD) diets for 12 weeks. Mice were exposed to lifetime Pb (50 ppm) through drinking water. HFD was associated with increased body mass and glucose intolerance. Both HFD and Pb increased fasting glucose and serum leptin levels. Pb and HFD each reduced trabecular bone quality and together had a further detrimental effect on these bone parameters. Mechanical bone properties of strength were depressed in Pb-exposed bones, but HFD had no significant effect. Both Pb and HFD altered progenitor cell differentiation, promoting osteoclastogenesis and increasing adipogenesis while suppressing osteoblastogenesis. In support of this lineage shift being mediated through altered Wnt signaling, Pb and non-esterified fatty acids in MC3T3 cells increased in vitro PPAR-γ activity and inhibited β-catenin activity. Combining Pb and non-esterified fatty acids enhanced these effects. Pb and HFD produced selective deficits in bone accrual that were associated with alterations in progenitor cell activity that may involve reduced Wnt signaling. This study emphasizes the need to assess toxicants together with other risk factors relevant to human health and disease. Beier EE, Inzana JA, Sheu TJ, Shu L, Puzas JE, Mooney RA. 2015. Effects of combined exposure to lead and high-fat diet on bone quality in juvenile male mice. Environ Health Perspect 123:935–943; http://dx.doi.org/10.1289/ehp.1408581