Douchi Peptides VY and SFLLR Improve Glucose Homeostasis and Gut Dysbacteriosis in High-Fat Diet-Induced Insulin Resistant Mice.

Scope: 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.

Methods And Results: 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).

Conclusion: The study reveals the potential applications of peptides VY and SFLLR as a diet-based strategy for the prevention of type 2 diabetes.