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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。

Sex-specific effects of transgene on bone material properties, size, and shape in mice.

作者信息

Bermudez Beatriz, Brown Kenna C, Vahidi Ghazal, Ferreira Ruble Ana C, Heveran Chelsea M, Ackert-Bicknell Cheryl L, Sherk Vanessa D

机构信息

Department of Mechanical Engineering, University of Colorado Denver, Denver, CO 80204, United States.

Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States.

出版信息

JBMR Plus. 2024 Jan 10;8(4):ziad011. doi: 10.1093/jbmrpl/ziad011. eCollection 2024 Apr.

DOI:10.1093/jbmrpl/ziad011
PMID:38523667
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10958611/
Abstract

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 transgenic mice, which carry a gene responsible for encoding a ω-3 fatty acid desaturase that converts ω-6 to ω-3 fatty acids. Male and female positive mice () and negative littermates (WT) were given either a high-fat diet (HFD) or low-fat diet (LFD) at 4 wk of age for 16 wk. The transgene reduced fracture toughness in males. Additionally, male BMD, measured from DXA, decreased over the diet duration for HFD mice. In males, neither HFD feeding nor the presence of the transgene impacted cortical geometry, trabecular architecture, or whole-bone flexural properties, as detected by main group effects. In females, -LFD mice experienced increases in BMD compared to WT-LFD mice; however, cortical area, distal femur trabecular thickness, and cortical stiffness were reduced in 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, mediated fatty acid conversion was not able to mitigate the adverse effects of HFD on bone strength and accrual.

摘要

西方饮食在全球正变得越来越普遍。西方饮食中ω-6(欧米伽6)和ω-3(欧米伽3)脂肪酸含量高,与人类和动物的骨质流失有关。膳食脂肪并非完全相同;因此,了解特定膳食脂肪对骨骼的影响至关重要。我们旨在确定改变内源性ω-6:ω-3脂肪酸比例如何影响骨量积累、强度和骨折韧性。为实现这一目标,我们使用了转基因小鼠,其携带一个负责编码将ω-6转化为ω-3脂肪酸的ω-3脂肪酸去饱和酶的基因。在4周龄时,将雄性和雌性阳性小鼠()和阴性同窝小鼠(野生型)给予高脂饮食(HFD)或低脂饮食(LFD),持续16周。转基因降低了雄性小鼠的骨折韧性。此外,通过双能X线吸收法(DXA)测量,高脂饮食小鼠在饮食期间雄性骨密度降低。在雄性小鼠中,通过主要组效应检测,高脂饮食喂养和转基因的存在均未影响皮质几何形状、小梁结构或全骨弯曲特性。在雌性小鼠中,与野生型低脂饮食小鼠相比,转基因低脂饮食小鼠的骨密度增加;然而,与合并的野生型对照组相比,转基因小鼠的皮质面积、股骨远端小梁厚度和皮质硬度降低。然而,硬度的降低是由骨大小的减小引起的,而非材料特性的变化所致。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,介导的脂肪酸转化无法减轻高脂饮食对骨骼强度和骨量积累的不利影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/4ccb1f8abfad/ziad011f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/5a6bf28eba49/ziad011ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/d053f8573c6d/ziad011f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/f9d1d494e50b/ziad011f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/201e7c1df902/ziad011f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/68ef45196e15/ziad011f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/c98d2703312a/ziad011f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/b24fcb7f5ace/ziad011f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/4c205b84ceec/ziad011f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/4ccb1f8abfad/ziad011f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/5a6bf28eba49/ziad011ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/d053f8573c6d/ziad011f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/f9d1d494e50b/ziad011f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/201e7c1df902/ziad011f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/68ef45196e15/ziad011f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/c98d2703312a/ziad011f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/b24fcb7f5ace/ziad011f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/4c205b84ceec/ziad011f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f3/10958611/4ccb1f8abfad/ziad011f8.jpg

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