Department of Biochemical Science &Technology, National Taiwan University, Taipei, Taiwan.
School of Life Science, Undergraduate and Graduate Programs of Nutrition Science, National Taiwan Normal University, Taipei, Taiwan.
Life Sci. 2023 Nov 15;333:122180. doi: 10.1016/j.lfs.2023.122180. Epub 2023 Oct 15.
Obesity is the main cause of low-grade inflammation and oxidation, resulting in insulin resistance. This study aimed to investigate the effects of a seed peptide lunasin on glucose utilization in C2C12 myotubes and the metabolite profiles in obese mice.
C2C12 myotubes were challenged by palmitic acid (PA) to mimic the obese microenvironment and inflammation, cell vitality, and glucose utilization were determined. C57BL6/j mice were divided into low-fat diet (LF), high-fat diet (HF), and HF with intraperitoneally injected lunasin (HFL) groups. Glucose intolerance and metabolite profiles of the tissues were analyzed.
In vitro, C2C12 myotubes treated with lunasin showed decreased proinflammatory cytokines and increased cell vitality under palmitic acid conditions. Lunasin improved glucose uptake and glucose transporter 4 expression by activating insulin receptor substrate-1 and AKT phosphorylation. Next-generation sequencing revealed that lunasin regulates genes expression by promoting insulin secretion and decreasing oxidative stress. In vivo, HF mice showed increased tricarboxylic acid cycle and uric acid metabolites but decreased bile acids metabolites and specific amino acids. Lunasin intervention improved glucose intolerance and modulated metabolites associated with increased insulin sensitivity and decreased metabolic disorders.
This study is the first to reveal that lunasin is a promising regulator of anti-inflammation, anti-oxidation, and glucose utilization in myotubes and ameliorating glucose uptake and metabolite profiles in obese mice, contributing to glucose homeostasis and benefiting metabolic disorders.
肥胖是低度炎症和氧化的主要原因，导致胰岛素抵抗。本研究旨在探讨种子肽 lunasin 对 C2C12 肌管葡萄糖利用的影响及其在肥胖小鼠中的代谢物谱。
用棕榈酸（PA）刺激 C2C12 肌管模拟肥胖微环境，测定细胞活力和葡萄糖利用情况。将 C57BL6/j 小鼠分为低脂饮食（LF）、高脂饮食（HF）和腹腔注射 lunasin 的高脂饮食（HFL）组。分析葡萄糖耐量和组织代谢物谱。
在体外，lunasin 处理的 C2C12 肌管在棕榈酸条件下显示出减少的促炎细胞因子和增加的细胞活力。 lunasin 通过激活胰岛素受体底物-1 和 AKT 磷酸化来提高葡萄糖摄取和葡萄糖转运蛋白 4 的表达。下一代测序显示 lunasin 通过促进胰岛素分泌和减少氧化应激来调节基因表达。在体内，HF 小鼠表现出三羧酸循环和尿酸代谢物增加，但胆汁酸代谢物和特定氨基酸减少。 lunasin 干预改善了葡萄糖耐量，并调节了与增加胰岛素敏感性和减少代谢紊乱相关的代谢物。
本研究首次揭示 lunasin 是肌管抗炎、抗氧化和葡萄糖利用的有前途的调节剂，并改善肥胖小鼠的葡萄糖摄取和代谢物谱，有助于葡萄糖稳态并有益于代谢紊乱。
