Department of Food Science and Technology, Zhejiang University of Technology, Hangzhou 310014, China.
Nutrients. 2023 Jun 24;15(13):2863. doi: 10.3390/nu15132863.
Long-term hypercaloric intake such as a high-fat diet (HFD) could act as negative regulators on bone remodeling, thereby inducing bone loss and bone microarchitecture destruction. Currently, food-derived natural compounds represent a promising strategy to attenuate HFD-induced bone loss. We previously prepared a whey protein hydrolysate (WPH) with osteogenic capacity. In this study, we continuously isolated and identified an osteogenic and antioxidant octapeptide TPEVDDA from WPH, which significantly promoted the alkaline phosphatase activities on MC3T3-E1 cells and exerted DPPH radical scavenging capacity. We then established an HFD-fed obese mice model with significantly imbalanced redox status and reduced bone mass and further evaluated the effects of different doses of WPH on ameliorating the HFD-induced bone loss and oxidative damages. Results showed that the administration of 2% and 4% WPH for 12 weeks significantly restored perirenal fat mass, improved serum lipid levels, reduced oxidative stress, and promoted the activity of antioxidant enzymes; meanwhile, WPH significantly preserved bone mass and bone mechanical properties, attenuated the degradation of trabecular microstructure, and regulated serum bone metabolism biomarkers. The protein levels of Runx2, Nrf2, and HO-1, as well as the phosphorylation level of GSK-3β in tibias, were notably activated by WPH. Overall, we found that the potential mechanism of WPH on ameliorating the HFD-induced bone loss mainly through its antioxidant and osteogenic capacity by activating Runx2 and GSK-3β/Nrf2 signaling pathway, demonstrating the potential of WPH to be used as a nutritional strategy for obesity and osteoporosis.
长期高热卡摄入，如高脂肪饮食（HFD），可能作为骨重建的负调节剂，从而导致骨丢失和骨微结构破坏。目前，来源于食物的天然化合物代表了一种有前途的策略，可以减轻 HFD 诱导的骨丢失。我们之前制备了具有成骨能力的乳清蛋白水解物（WPH）。在这项研究中，我们从 WPH 中连续分离和鉴定出一种具有成骨和抗氧化能力的八肽 TPEVDDA，它能显著促进 MC3T3-E1 细胞的碱性磷酸酶活性，并具有 DPPH 自由基清除能力。然后，我们建立了一个 HFD 喂养的肥胖小鼠模型，该模型具有明显失衡的氧化还原状态和减少的骨量，并进一步评估了不同剂量的 WPH 对改善 HFD 诱导的骨丢失和氧化损伤的影响。结果表明，12 周连续给予 2%和 4%的 WPH 可显著恢复肾周脂肪量，改善血清脂质水平，降低氧化应激，促进抗氧化酶的活性；同时，WPH 可显著保留骨量和骨力学性能，减轻小梁微结构的降解，并调节血清骨代谢生物标志物。WPH 显著激活了胫骨中 Runx2、Nrf2 和 HO-1 的蛋白水平以及 GSK-3β的磷酸化水平。总的来说，我们发现 WPH 通过其抗氧化和成骨能力来改善 HFD 诱导的骨丢失的潜在机制主要是通过激活 Runx2 和 GSK-3β/Nrf2 信号通路，这表明 WPH 具有作为肥胖和骨质疏松症的营养策略的潜力。
