Soymorphin-5, a soy-derived μ-opioid peptide, decreases glucose and triglyceride levels through activating adiponectin and PPARα systems in diabetic KKAy mice

• Published in: American journal of physiology: endocrinology and metabolism 2012-02, Vol.302 (4), p.E433-E440
• Main Authors: Yamada, Yuko, Muraki, Aya, Oie, Mariko, Kanegawa, Norimasa, Oda, Ayako, Sawashi, Yurina, Kaneko, Kentaro, Yoshikawa, Masaaki, Goto, Tsuyoshi, Takahashi, Nobuyuki, Kawada, Teruo, Ohinata, Kousaku
• Format: Article
• Language: English
• Subjects: Acyl-CoA Oxidase - biosynthesis; Adiponectin - agonists; Animals; Blood Glucose - drug effects; Carnitine O-Palmitoyltransferase - metabolism; Diabetes Mellitus, Type 2 - metabolism; Fatty Acids - metabolism; Hyperglycemia - drug therapy; Hypoglycemic Agents - pharmacology; Hypolipidemic Agents - pharmacology; Insulin - blood; Ion Channels - biosynthesis; Liver - chemistry; Liver - drug effects; Male; Mice; Mitochondrial Proteins - biosynthesis; Opioid Peptides - pharmacology; Peptide Fragments - pharmacology; PPAR alpha - agonists; Receptors, Adiponectin - biosynthesis; Soybean Proteins - pharmacology; Triglycerides - antagonists & inhibitors; Triglycerides - blood; Uncoupling Protein 2
• ISSN: 1522-1555
• DOI: 10.1152/ajpendo.00161.2011

Soymorphin-5 (YPFVV) derived from soybean β-conglycinin β-subunit is a μ-opioid agonist peptide having anxiolytic-like activity. Here, we show that soymorphin-5 improves glucose and lipid metabolism after long-term oral administration to KKAy mice, a type 2 diabetes model animal. Soymorphin-5 inhibited hyperglycemia without an increase in plasma insulin levels in KKAy 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)α pathway and fatty acid β-oxidation. The expressions of the mRNA of PPARα 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 μ-opioid and anxiolytic-like activities did not decrease blood glucose levels in KKAy mice. These results suggest that μ-opioid peptide soymorphin-5 improves glucose and lipid metabolism via activation of the adiponectin and PPARα system and subsequent increases of β-oxidation and energy expenditure in KKAy mice.