Suryaningtyas Indyaswan T, Marasinghe Chathuri K, Lee Bonggi, Je Jae-Young
Department of Food and Nutrition, Pukyong National University, Busan, Republic of Korea; Research Center for Food Technology and Processing, National Research and Innovation Agency, Yogyakarta, Indonesia.
Department of Food and Nutrition, Pukyong National University, Busan, Republic of Korea.
J Nutr Biochem. 2025 Feb;136:109791. doi: 10.1016/j.jnutbio.2024.109791. Epub 2024 Oct 28.
The bioactive peptides PIISVYWK (P1) and FSVVPSPK (P2), derived from the blue mussel Mytilus edulis, exhibit significant benefits in combating obesity, oxidative stress, and inflammation. This study demonstrates that these peptides inhibit the differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) into adipocytes by downregulating the adipogenic transcription factors peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP-1). Furthermore, P1 and P2 reduce lipogenesis and enhance lipolysis through the activation of AMP-activated protein kinase (AMPK) and hormone-sensitive lipase (HSL). These peptides also decrease intracellular reactive oxygen species (ROS) generation during adipogenesis and inhibit the mitogen-activated protein kinase (MAPK) pathway, thereby reducing inflammation. The involvement of heme oxygenase-1 (HO-1) in this mechanism is confirmed by the reversal of these effects upon HO-1 inhibition. In vivo, oral administration of P1 and P2 in high-fat diet (HFD) obese mice prevents weight gain, reduces adipose tissue accumulation, lowers adipogenic and lipogenic biomarkers, improves serum cholesterol levels, enhances lipolysis, and decreases pro-inflammatory cytokine production. These findings suggest that P1 and P2 peptides may effectively prevent obesity and related metabolic disorders by activating the HO-1/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
源自蓝贻贝紫贻贝的生物活性肽PIISVYWK（P1）和FSVVPSPK（P2）在对抗肥胖、氧化应激和炎症方面具有显著益处。本研究表明，这些肽通过下调脂肪生成转录因子过氧化物酶体增殖物激活受体γ（PPARγ）、CCAAT/增强子结合蛋白α（C/EBPα）和固醇调节元件结合蛋白1（SREBP-1）来抑制骨髓间充质干细胞（BMMSC）向脂肪细胞的分化。此外，P1和P2通过激活AMP激活的蛋白激酶（AMPK）和激素敏感性脂肪酶（HSL）来减少脂肪生成并增强脂肪分解。这些肽还减少脂肪生成过程中细胞内活性氧（ROS）的产生，并抑制丝裂原活化蛋白激酶（MAPK）途径，从而减轻炎症。血红素加氧酶-1（HO-1）在这一机制中的参与通过HO-1抑制后这些作用的逆转得到证实。在体内，对高脂饮食（HFD）肥胖小鼠口服P1和P2可防止体重增加、减少脂肪组织积累、降低脂肪生成和脂肪生成生物标志物、改善血清胆固醇水平、增强脂肪分解并减少促炎细胞因子的产生。这些发现表明，P1和P2肽可能通过激活HO-1/核因子红细胞2相关因子2（Nrf2）途径有效预防肥胖和相关代谢紊乱。
