高脂饮食诱发肥胖症小鼠骨质脆弱与 2 型糖尿病无关

IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Calcified Tissue International Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI:10.1007/s00223-024-01252-x
Sasidhar Uppuganti, Amy Creecy, Daniel Fernandes, Kate Garrett, Kara Donovan, Rafay Ahmed, Paul Voziyan, Elizabeth Rendina-Ruedy, Jeffry S Nyman
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引用次数: 0

摘要

肥胖和 2 型糖尿病(T2D)是脆性骨折的风险因素。目前还不清楚这种风险的升高是由于偏向肥胖的饮食,还是由于肥胖经常导致的糖尿病。因此,我们假设,无论小鼠是否出现明显的 T2D,以高脂肪饮食(45% 千卡;HFD)喂养的小鼠的骨骼抗骨折能力都低于以类似的对照饮食(10% 千卡;LFD)喂养的小鼠。16周大的雄性NON/ShiLtJ小鼠(对T2D有抵抗力)和年龄匹配的雄性NONcNZO10/LtJ小鼠(易患T2D)接受对照组低脂饮食或高脂饮食21周。与 NZO10 小鼠相比,HFD 在更大程度上增加了 ShiLtJ 小鼠的体重,而 NZO10 小鼠的血糖水平明显高于 ShiLtJ 小鼠。因此,NZO10 小鼠的糖化血红蛋白 A1c(HbA1c)水平超过了 10%,但 ShiLtJ 小鼠的糖化血红蛋白 A1c 水平仍低于 6%。饮食对 HbA1c 没有影响。高氟饮食会降低两个品系小鼠股骨远端干骺端的骨小梁数量和骨体积分数(显微计算机断层扫描或μCT)。对于股骨中段干骺端,HFD显著降低了两个品系的屈服力矩(通过三点弯曲进行机械测试),但不影响横截面骨面积、皮质厚度和皮质组织矿物质密度(μCT)。此外,饮食对屈服力矩的影响与股骨干骺端中段的结构阻力无关,这表明高脂饮食对骨基质的特征有负面影响。然而,无论是拉曼光谱还是高级糖化终产物检测,都无法确定 HFD 是如何影响基质的。HFD 还降低了皮质骨对裂缝生长的抵抗力(其他股骨的断裂韧性测试),而 HFD 则降低了两个品系 L6 椎体的极限力(压缩测试)。总之,抗糖尿病和易患糖尿病的小鼠都会出现与高脂饮食相关的骨强度下降,这表明高脂饮食会对骨骼产生有害影响,但不一定会导致高血糖。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Bone Fragility in High Fat Diet-induced Obesity is Partially Independent of Type 2 Diabetes in Mice.

Bone Fragility in High Fat Diet-induced Obesity is Partially Independent of Type 2 Diabetes in Mice.

Obesity and type 2 diabetes (T2D) are risk factors for fragility fractures. It is unknown whether this elevated risk is due to a diet favoring obesity or the diabetes that often occurs with obesity. Therefore, we hypothesized that the fracture resistance of bone is lower in mice fed with a high fat diet (45% kcal; HFD) than in mice that fed on a similar, control diet (10% kcal; LFD), regardless of whether the mice developed overt T2D. Sixteen-week-old, male NON/ShiLtJ mice (resistant to T2D) and age-matched, male NONcNZO10/LtJ (prone to T2D) received a control LFD or HFD for 21 weeks. HFD increased the bodyweight to a greater extent in the ShiLtJ mice compared to the NZO10 mice, while blood glucose levels were significantly higher in NZO10 than in ShiLtJ mice. As such, the glycated hemoglobin A1c (HbA1c) levels exceeded 10% in NZO10 mice, but it remained below 6% in ShiLtJ mice. Diet did not affect HbA1c. HFD lowered trabecular number and bone volume fraction of the distal femur metaphysis (micro-computed tomography or μCT) in both strains. For the femur mid-diaphysis, HFD significantly reduced the yield moment (mechanical testing by three-point bending) in both strains but did not affect cross-sectional bone area, cortical thickness, nor cortical tissue mineral density (μCT). Furthermore, the effect of diet on yield moment was independent of the structural resistance of the femur mid-diaphysis suggesting a negative effect of HFD on characteristics of the bone matrix. However, neither Raman spectroscopy nor assays of advanced glycation end-products identified how HFD affected the matrix. HFD also lowered the resistance of cortical bone to crack growth in only the diabetic NZO10 mice (fracture toughness testing of other femur), while HFD reduced the ultimate force of the L6 vertebra in both strains (compression testing). In conclusion, the HFD-related decrease in bone strength can occur in mice resistant and prone to diabetes indicating that a diet high in fat deleteriously affects bone without necessarily causing hyperglycemia.

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来源期刊
Calcified Tissue International
Calcified Tissue International 医学-内分泌学与代谢
CiteScore
8.00
自引率
2.40%
发文量
112
审稿时长
4-8 weeks
期刊介绍: Calcified Tissue International and Musculoskeletal Research publishes original research and reviews concerning the structure and function of bone, and other musculoskeletal tissues in living organisms and clinical studies of musculoskeletal disease. It includes studies of cell biology, molecular biology, intracellular signalling, and physiology, as well as research into the hormones, cytokines and other mediators that influence the musculoskeletal system. The journal also publishes clinical studies of relevance to bone disease, mineral metabolism, muscle function, and musculoskeletal interactions.
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