Soymorphin-5, a soy-derived ja-opioid peptide, decreases glucose and triglyceride levels through activating adiponectin and PPARalpha systems in diabetic KKA~y mice

摘要

Soymorphin-5 (YPFVV) derived from soybean beta-conglycinin beta-subunit is a (x-opioid agonist peptide having anxiolytic-like activity. Here, we show that soymorphin-5 improves glucose and lipid metabolism after long-term oral administration to KKA~y mice, a type 2 diabetes model animal. Soymorphin-5 inhibited hyperglycemia without an increase in plasma insulin levels in KKA~y mice. Soymorphin-5 also decreased plasma and liver triglyceride (TG) levels and liver weight, suggesting that soymorphin-5 improved lipid metabolism. Soymorphin-5 increased plasma adiponectin concentration and liver mRNA expression of AdipoR2, a subtype of adiponectin receptor that is involved in stimulating the peroxisome proliferator-activated receptor (PPAR)alpha pathway and fatty acid beta-oxidation. The expressions of the mRNA of PPARa and its target genes acyl-CoA oxidase, carnitine palmitoyltransferase 1 A, and uncoupling protein-2, in the liver were also increased after oral administration of soymorphin-5. Furthermore, des-Tyr-soymorphin-5 (PFVV) without (x-opioid and anxiolytic-like activities did not decrease blood glucose levels in KKA~y mice. These results suggest that (x-opioid peptide soymorphin-5 improves glucose and lipid metabolism via activation of the adiponectin and PPARa system and subsequent increases of (3-oxidation and energy expenditure in KKA~y mice.