The State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, No. 130 Meilong Road, Xuhui District, Shanghai, 200237, China.
J Food Sci. 2021 Mar;86(3):1105-1113. doi: 10.1111/1750-3841.15625. Epub 2021 Feb 13.
Nonalcoholic fatty liver disease (NAFLD) is a metabolic syndrome, whose main characteristics are excessive lipid accumulation and oxidative stress. Major royal jelly proteins (MRJPs) is a kind of water-soluble protein, which is abundant in royal jelly (RJ). The aim of this study was to evaluate the effect of MRJPs on lipid accumulation and oxidative stress of liver cells. Here, we first optimized the conditions for extracting MRJPs from RJ and identified the extraction effect and product by SDS-PAGE. Then, we used oleic acid (OA) of 1.0 mM to induce hepatocytes for 24 hr to establish a stable cell models of lipid accumulation, and we found that pre-administration (24 hr) of MRJPs (0.2, 0.5, and 1.0 g/L) could significantly reduce the lipid drop content and triglyceride level in the model cells, and simultaneously reduce the alanine aminotransferase and aspertate aminotransferase levels in the cell culture supernatant. In addition, pre-incubation (24 hr) with MRJPs (0.2, 0.5, and 1.0 g/L) could restore superoxide dismutase (SOD) level and mitochondrial membrane potential as compared with OA group. Furthermore, MRJPs administration significantly upregulated the expression of Silent Information Regulator 2 Associated Protein 3, mitochondrial superoxide dismutase (SOD2), and cytochrome c oxidase subunit IV in OA-treated HepG2 cells. The study for the first time provides evidences on the lipid-lowering effect of MRJPs at the cellular level, which can further provide support for the development and application of polypeptide drugs in the future, and can also provide a choice for the prevention and treatment of liver metabolic diseases represented by NAFLD. PRACTICAL APPLICATION: Our study proved that MRJPs had substantial preventing effect on OA-induced lipid accumulation and mitochondrial dysfunction in HepG2 cells. This research can further provide theoretical support for the development and application of peptide drugs in the future. Besides, it can not only further broaden our understanding of NAFLD and other diseases, but also provide ideas for research on oxidative stress and lipid accumulation in the body.
非酒精性脂肪性肝病（NAFLD）是一种代谢综合征，其主要特征是脂质蓄积过多和氧化应激。主要蜂王浆蛋白（MRJPs）是一种水溶性蛋白质，在蜂王浆（RJ）中含量丰富。本研究旨在评估 MRJPs 对肝细胞脂质蓄积和氧化应激的影响。我们首先优化了从 RJ 中提取 MRJPs 的条件，并通过 SDS-PAGE 鉴定了提取效果和产物。然后，我们使用 1.0mM 的油酸（OA）诱导肝细胞 24 小时，建立稳定的脂质蓄积细胞模型，发现预给药（24 小时）MRJPs（0.2、0.5 和 1.0g/L）可显著降低模型细胞中的脂滴含量和甘油三酯水平，同时降低细胞培养上清液中的丙氨酸氨基转移酶和天门冬氨酸氨基转移酶水平。此外，MRJPs（0.2、0.5 和 1.0g/L）孵育（24 小时）可恢复与 OA 组相比的超氧化物歧化酶（SOD）水平和线粒体膜电位。此外，MRJPs 给药可显著上调 OA 处理的 HepG2 细胞中沉默信息调节因子 2 相关蛋白 3、线粒体超氧化物歧化酶（SOD2）和细胞色素 c 氧化酶亚基 IV 的表达。该研究首次在细胞水平上提供了 MRJPs 降脂作用的证据，这可为未来多肽药物的开发和应用提供支持，也可为以非酒精性脂肪性肝病（NAFLD）为代表的肝脏代谢性疾病的防治提供选择。实际应用：本研究证明 MRJPs 对 HepG2 细胞中 OA 诱导的脂质蓄积和线粒体功能障碍具有显著的预防作用。本研究可为未来肽类药物的开发和应用提供进一步的理论支持。此外，它不仅可以进一步拓宽我们对 NAFLD 等疾病的认识，还可以为体内氧化应激和脂质蓄积的研究提供思路。
