College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou, 310058, China.
Innovation Center of Yangtze River Delta, Zhejiang University, Jiashan, 314100, China.
Mol Nutr Food Res. 2023 May;67(10):e2200681. doi: 10.1002/mnfr.202200681. Epub 2023 Apr 4.
Two peptides VY (Val-Tyr) and SFLLR (Ser-Phe-Leu-Leu-Arg) are recently identified from soy-fermented douchi with hypoglycemic activity in cells. The study aims to understand their potential effects on glucose metabolism and insulin sensitivity as well as their mechanisms of action in a high-fat diet (HFD) induced insulin resistant model.
C57BL/6 mice are fed HFD for 8 weeks, followed by peptide supplementation (doses: 10 and 50 mg kg body weight) for 8 weeks. Peptides supplementation, especially SFLLR, reduces body weight gain, insulin resistance, hyperglycemia, inflammation, liver injury, and lipid accumulation. In both muscle and liver, both peptides activate glycogen synthase (GS), the key enzyme for glycogen synthesis, and also inhibit phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6PC), two rate-limiting enzymes for gluconeogenesis, via insulin and AMPK (5'-adenosine monophosphate-activated protein kinase) signaling pathways. Furthermore, VY and SFLLR supplementation reverse HFD-induced gut dysbacteriosis by decreasing the abundance of Enterococcus, Oscillibacter, and Deferribacter, and also increase the abundances of Alistipes, Lactobacillus, Faecalibaculum, Akkermansia, and Bifidobacterium (usually beneficial in the intestine).
The study reveals the potential applications of peptides VY and SFLLR as a diet-based strategy for the prevention of type 2 diabetes.
两种肽 VY（缬氨酸-酪氨酸）和 SFLLR（丝氨酸-苯丙氨酸-亮氨酸-精氨酸）最近从发酵豆酱中被鉴定出来，具有细胞内降血糖活性。本研究旨在了解它们在高脂肪饮食（HFD）诱导的胰岛素抵抗模型中对葡萄糖代谢和胰岛素敏感性的潜在影响及其作用机制。
C57BL/6 小鼠喂食 HFD 8 周，然后补充肽（剂量：10 和 50 mg/kg 体重）8 周。肽补充，特别是 SFLLR，可降低体重增加、胰岛素抵抗、高血糖、炎症、肝损伤和脂质积累。在肌肉和肝脏中，两种肽都通过胰岛素和 AMPK（5'-单磷酸腺苷激活蛋白激酶）信号通路激活糖原合成的关键酶糖原合酶（GS），并抑制磷酸烯醇丙酮酸羧激酶（PEPCK）和葡萄糖 6-磷酸酶（G6PC），这两种酶是糖异生的限速酶。此外，VY 和 SFLLR 补充通过降低肠杆菌属、摆动杆菌属和脱硫弧菌属的丰度，同时增加 Alistipes、乳杆菌属、粪杆菌属、阿克曼氏菌属和双歧杆菌属（通常在肠道中有益），逆转 HFD 诱导的肠道菌群失调。
该研究揭示了肽 VY 和 SFLLR 作为一种基于饮食的策略，用于预防 2 型糖尿病的潜在应用。
