Brown Kenna, Vahidi Ghazal, Hislop Brady D, Moody Maya, Watson Steven, Welhaven Hope D, Behzad Ramina, Paton Kat O, Karim Lamya, June Ronald K, Martin Stephen A, Heveran Chelsea M
Department of Mechanical & Industrial Engineering, Montana State University, Bozeman, MT, USA.
Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT, USA.
Commun Biol. 2025 Jun 3;8(1):850. doi: 10.1038/s42003-025-08263-w.
The elderly are at increased risk of bone fracture and more often consume poor quality diets, such as high-fat diet (HFD). We hypothesized that HFD exacerbates the loss of bone fracture resistance in aging. Female and male 5-month and 22-month C57BL/6JN mice were fed moderate HFD (45%) or low-fat diet (10%) for 8 weeks. All HFD groups showed disrupted glucose metabolism. Aging and HFD lowered bone fracture toughness, while aging alone reduced bone strength. Raman Spectroscopy demonstrated that aging and HFD differently impact bone matrix. Aging altered matrix properties but the effect depended on sex. Both sexes had higher carbonate content and altered collagen structure (I1670/I1690) with age but males also had increased crystallinity. HFD decreased mineral maturity (i.e., crystallinity) as well as altered collagen structure in females but not males. Untargeted metabolomics revealed that cortical tissue metabolism was dysregulated with aging and HFD. Aging and HFD affected pathways related to cellular function and viability, or glucose regulation, respectively. In aging mice, HFD also impacted osteoclast and adipocyte abundance and osteocyte viability in both sexes. Together, these data demonstrate that HFD exacerbates the loss of bone matrix quality and fracture resistance in aging C57BL/6JN mice.
老年人骨折风险增加，且更常食用低质量饮食，如高脂饮食（HFD）。我们假设高脂饮食会加剧衰老过程中骨折抵抗能力的丧失。对5个月和22个月大的雌性和雄性C57BL/6JN小鼠喂食中等量高脂饮食（45%）或低脂饮食（10%），持续8周。所有高脂饮食组均出现葡萄糖代谢紊乱。衰老和高脂饮食会降低骨折韧性，而仅衰老会降低骨强度。拉曼光谱显示，衰老和高脂饮食对骨基质的影响不同。衰老会改变基质特性，但效果取决于性别。随着年龄增长，两性的碳酸盐含量均升高，胶原蛋白结构改变（I1670/I1690），但雄性的结晶度也增加。高脂饮食会降低雌性而非雄性的矿物质成熟度（即结晶度），并改变胶原蛋白结构。非靶向代谢组学显示，随着衰老和高脂饮食，皮质组织代谢失调。衰老和高脂饮食分别影响与细胞功能和活力或葡萄糖调节相关的通路。在衰老小鼠中，高脂饮食还会影响两性的破骨细胞和脂肪细胞丰度以及骨细胞活力。总之，这些数据表明，高脂饮食会加剧衰老的C57BL/6JN小鼠骨基质质量和骨折抵抗能力的丧失。
