Whey Protein Hydrolysate Ameliorated High-Fat-Diet Induced Bone Loss via Suppressing Oxidative Stress and Regulating GSK-3β/Nrf2 Signaling Pathway

• Published in: Nutrients 2023-06, Vol.15 (13), p.2863
• Main Authors: Bu, Tingting, Huang, Ju, Yu, Yue, Sun, Peilong, Yang, Kai
• Format: Article
• Language: English
• Subjects: Alkaline phosphatase; Animals; Antioxidants; Antioxidants - pharmacology; Body fat; Bone loss; Bone mass; Bone remodeling; Bone turnover; Bones; Cbfa-1 protein; Computer architecture; Core Binding Factor Alpha 1 Subunit - metabolism; Density; Diet; Diet, High-Fat - adverse effects; Energy consumption; Enzymes; Ethylenediaminetetraacetic acid; Glycogen Synthase Kinase 3 beta - metabolism; High fat diet; High protein diet; Hydrolysates; Kinases; Lipids; Mechanical properties; Metabolism; Mice; NF-E2-Related Factor 2 - metabolism; Obesity; Osteoporosis; Oxidative Stress; Peptides; Phosphatase; Phosphatases; Phosphorylation; Physiological aspects; Protein hydrolysates; Protein Hydrolysates - metabolism; Protein Hydrolysates - pharmacology; Protein Hydrolysates - therapeutic use; Protein turnover; Proteins; runt-related transcription factor 2; Scavenging; Signal Transduction; Tumor necrosis factor-TNF; Type 2 diabetes; Whey; Whey - metabolism; Whey protein; whey protein hydrolysate
• ISSN: 2072-6643; 2072-6643
• 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.