Fat-1转基因对小鼠骨骼材料特性、大小和形状的性别特异性影响

IF 3.4 Q2 ENDOCRINOLOGY & METABOLISM
JBMR Plus Pub Date : 2024-01-10 DOI:10.1093/jbmrpl/ziad011
Beatriz Bermudez, Kenna Brown, G. Vahidi, Ana C F Ruble, Chelsea M Heveran, Cheryl L Ackert-Bicknell, Vanessa Sherk
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引用次数: 0

摘要

西式饮食在全世界越来越普遍。西方饮食中含有大量欧米伽 6(ω-6)和欧米伽 3(ω-3)脂肪酸,与人类和动物的骨质流失有关。膳食脂肪并不完全相同;因此,了解特定膳食脂肪对骨骼的影响至关重要。我们的目的是确定改变ω-6:ω-3 脂肪酸的内源性比例会如何影响骨骼的累积、强度和断裂韧性。为了实现这一目标,我们使用了携带ω-3脂肪酸去饱和酶编码基因的Fat-1转基因小鼠,该基因可将ω-6脂肪酸转化为ω-3脂肪酸。雌雄Fat-1阳性小鼠(Fat-1)和Fat-1阴性同窝小鼠(WT)在4周龄时被给予高脂饮食(HFD)或低脂饮食(LFD),持续16周。Fat-1转基因降低了雄性动物的骨折韧性。此外,通过双能X射线吸收测定法(DXA)测量的雄性骨矿物质密度(BMD)在HFD小鼠的饮食持续时间内有所下降。在雄性小鼠中,HFD喂养和Fat-1转基因的存在都不会影响皮质几何形状、骨小梁结构或全骨挠曲特性,这是由主组效应检测到的。在雌性小鼠中,与 WT-LFD 小鼠相比,Fat-1-LFD 小鼠的 BMD 增加了,但与 WT 对照组相比,Fat-1 小鼠的皮质面积、股骨远端小梁厚度和皮质硬度降低了。然而,刚度的降低是由骨骼尺寸的减小引起的,而不是由材料特性的变化引起的。总之,这些结果表明,内源性ω-6:ω-3 脂肪酸比例以性别依赖的方式影响骨材料特性。此外,Fat-1介导的脂肪酸转换并不能减轻高密度脂蛋白胆固醇对骨质强度和累积的不利影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sex-specific effects of Fat-1 transgene on bone material properties, size, and shape in mice
Western diets are becoming increasingly common around the world. Western diets have high omega 6 (ω-6) and omega 3 (ω-3) fatty acids and are linked to bone loss in humans and animals. Dietary fats are not created equal; therefore, it is vital to understand the effects of specific dietary fats on bone. We aimed to determine how altering the endogenous ratios of ω-6:ω-3 fatty acids impacts bone accrual, strength, and fracture toughness. To accomplish this, we used the Fat-1 transgenic mice, which carry a gene responsible for encoding an ω-3 fatty acid desaturase that converts ω-6 to ω-3 fatty acids. Male and female Fat-1 positive mice (Fat-1) and Fat-1 negative littermates (WT) were given either a high-fat diet (HFD) or low-fat diet (LFD) at 4 weeks of age for 16 weeks. The Fat-1 transgene reduced fracture toughness in males. Additionally, male bone mineral density (BMD), measured from dual-energy x-ray absorptiometry (DXA), decreased over the diet duration for HFD mice. In males, neither HFD feeding nor the presence of the Fat-1 transgene impacted cortical geometry, trabecular architecture, or whole-bone flexural properties, as detected by main group effects. In females, Fat-1-LFD mice experienced increases in BMD compared to WT-LFD mice, however, cortical area, distal femur trabecular thickness, and cortical stiffness were reduced in Fat-1 mice compared to pooled WT controls. However, reductions in stiffness were caused by a decrease in bone size and were not driven by changes in material properties. Together, these results demonstrate that the endogenous ω-6:ω-3 fatty acid ratio influences bone material properties in a sex-dependent manner. In addition, Fat-1 mediated fatty acid conversion was not able to mitigate the adverse effects of HFD on bone strength and accrual.
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来源期刊
JBMR Plus
JBMR Plus Medicine-Orthopedics and Sports Medicine
CiteScore
5.80
自引率
2.60%
发文量
103
审稿时长
8 weeks
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