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

Abstract

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.

The Role of Food Peptides in Lipid Metabolism during Dyslipidemia and Associated Health Conditions

“…The PPARα-mediated signaling events will particularly promote hepatic fatty acid metabolism and energy expenditure whereas upregulation of SREBP gene would enhance cholesterol metabolism. Similar PPARα-mediated modulation of lipogenic gene expression was reported in diabetic KKAy mice that received soymorphin-5 (YPFVV), a pentapeptide derived from the β-subunit of soybean β-conglycinin [26]. The lipogenic gene regulation induced by soymorphin-5 was associated with hypolipidemic effects including decrease in plasma and liver TG, decrease in liver weight and increase in plasma adiponectin in the diabetic mice [26].…”

Dietary Soybean Peptides Containing a Low-Molecular Fraction Can Lower Serum and Liver Triglyceride Levels in Rats

“…A synthetic peptide (molecular weight, 2271) corresponding to the specific sequence of b-conglycinin was also reported to promote the uptake and degradation of LDL in the same cell line (28). Soymorphin-5 (YPFVV) derived from b-conglycinin may lower plasma and liver triglyceride levels via the activation of adiponectin and PPARa pathways in KK-A y mice (18). All the above-mentioned peptides originated from b-conglycinin, which is a major protein fraction of soybean that elicits improvements in triglyceride metabolism (10,11).…”

“…Therefore, LD may modulate triglyceride metabolism and contains the component(s) responsible for the hypotriglyceridemic activity of soybean protein. Soybean pentapeptides (18) and oligopeptides (19) have been recently implicated as the components responsible for the triglyceride-lowering effect of soybeans. However, the particular peptides in soybean protein responsible for the triglyceride-lowering effect have not been identified.…”

Relationship Between the Consumption of Soy and Its Derivatives During Critical Periods of Development and in Adulthood and Endocrine-Metabolic Disorders

“…The studies have shown adverse effects on Vieira et al J Endocrinol Metab. 2017;7(5):135-140 these hormones, having increased levels of adiponectin [37][38][39][40], and decreased levels of leptin [33,35,37,41]. However, there is divergence between these findings, being pointed by some authors the increased circulating leptin and decreased adiponectin [42,43].…”