Amelioration of High Fat Diet-Induced Obesity in Rat by Short Chain Pyroglutamyl Peptides in Japanese Salted Fermented Soy Paste (Miso)

Japanese salted fermented soybean paste (miso) is used as seasonings for traditional Japanese dishes. These products still play important roles in the modern dietary habits of Japanese, while consumption of these products has decreased approximately to 30-50% of consumption since 1975. Miso is produced by a fungi (Aspergillus oryzae) starter, referred to koji. A. oryzae produces a strong protease including both endoproteinases and exopeptidases. Thus, these products contain short chain peptides in addition to free amino acids. However, little was known of their structure and biological functions due to difficulty in isolation. In the present study, pyroglutamyl peptides present in miso were identified by a liquid chromatography-tandem mass spectrometry (LC-MS/MS), detecting precursor ions, which generated immonium ion of pyroglutamyl residue (m/z 84). By using this method, 13 pyroglutamyl peptides were identified in four types of miso. Administration of the water extract prepared from 0.6 g soybean miso/kg body weight/day significantly suppressed high fat diet-induced obesity. A similar effect was exerted by the hydrophobic pyroglutamyl peptide fraction, including pyroglutamyl proline (pEP), pEV, pEI, and pEL. Administration of a mixture of synthetic pEP, pEV, pEI, and pEL in a ratio to that in miso or pEL alone also suppressed the weight gain in a dose dependent manner. It has been demonstrated that high fat diet-induced small intestinal dysbiosis plays critical role in inducing obesity. pEL has been demonstrated to attenuate high fat diet-induced dysbiosis via enhancing secretion of host antimicrobial peptide into lumen. These results suggest that the short-chain hydrophobic pyroglutamyl peptides present in miso are effective in suppressing high fat diet-induced obesity via normalizing dysbiosis.