OBJECTIVE Obesity and osteoarthritis (OA) are 2 major public health issues affecting millions of people worldwide. Whereas parental obesity affects the predisposition to diseases such as cancer or diabetes in children, transgenerational influences on musculoskeletal conditions such as OA are poorly understood. This study was undertaken to assess the intergenerational effects of a parental/grandparental high-fat diet on the metabolic and skeletal phenotype, systemic inflammation, and predisposition to OA in 2 generations of offspring in mice. METHODS Metabolic phenotype and predisposition to OA were investigated in the first and second (F1 and F2) generations of offspring (n = 10-16 mice per sex per diet) bred from mice fed a high-fat diet (HFD) or a low-fat control diet. OA was induced by destabilizing the medial meniscus. OA, synovitis, and adipose tissue inflammation were determined histologically, while bone changes were measured using micro-computed tomography. Serum and synovial cytokines were measured by multiplex assay. RESULTS Parental high-fat feeding showed an intergenerational effect, with inheritance of increased weight gain (up to 19% in the F1 generation and 9% in F2), metabolic imbalance, and injury-induced OA in at least 2 generations of mice, despite the fact that the offspring were fed the low-fat diet. Strikingly, both F1 and F2 female mice showed an increased predisposition to injury-induced OA (48% higher predisposition in F1 and 19% in F2 female mice fed the HFD) and developed bone microarchitectural changes that were attributable to parental and grandparental high-fat feeding. CONCLUSION The results of this study reveal a detrimental effect of parental HFD and obesity on the musculoskeletal integrity of 2 generations of offspring, indicating the importance of further investigation of these effects. An improved understanding of the mechanisms involved in the transmissibility of diet-induced changes through multiple generations may help in the development of future therapies that would target the effects of obesity on OA and related conditions.

中文翻译：

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饮食诱导的肥胖、代谢失衡和骨关节炎在小鼠中的代际传播。

目标肥胖和骨关节炎 (OA) 是影响全球数百万人的两大公共卫生问题。虽然父母肥胖会影响儿​​童患癌症或糖尿病等疾病的倾向，但对 OA 等肌肉骨骼疾病的跨代影响却知之甚少。本研究旨在评估父母/祖父母高脂肪饮食对小鼠 2 代后代的代谢和骨骼表型、全身炎症和 OA 易感性的代际影响。方法 在高脂饮食 (HFD) 或低脂肪饮食的小鼠培育的第一代和第二代 (F1 和 F2) 后代 (n = 10-16 只小鼠/性别/饮食) 中研究代谢表型和 OA 易感性。脂肪控制饮食。OA 是通过使内侧半月板不稳定而引起的。OA，滑膜炎，和脂肪组织炎症是通过组织学确定的，而骨骼变化是使用微型计算机断层扫描测量的。通过多重测定法测量血清和滑膜细胞因子。结果 父母高脂喂养显示出代际效应，在至少 2 代小鼠中遗传了体重增加增加（F1 代高达 19%，F2 代高达 9%）、代谢失衡和损伤诱导的 OA，尽管后代被喂食低脂饮食的事实。引人注目的是，F1 和 F2 雌性小鼠对损伤性 OA 的易感性增加（喂食 HFD 的 F1 和 F2 雌性小鼠易感性增加 48% 和 19%），并且由于父母和祖父母的高脂肪而发生骨微结构变化喂养。结论 本研究结果揭示了父母 HFD 和肥胖对 2 代后代肌肉骨骼完整性的不利影响，表明进一步研究这些影响的重要性。更好地理解饮食引起的变化通过多代传递的机制可能有助于开发未来的疗法，这些疗法将针对肥胖对 OA 和相关疾病的影响。