The Novel Peptide Chm-273s Has Therapeutic Potential for Metabolic Disorders: Evidence from In Vitro Studies and High-Sucrose Diet and High-Fat Diet Rodent Models

Abstract

The aim of this study was to develop a novel peptide potentially applicable for the treatment of metabolic conditions, such as obesity and type 2 diabetes (T2D). We identified CHM-273S from the list of peptides from milk hydrolysate obtained by HPLC/MS-MS. In vitro analysis of primary murine fibroblasts indicated the potential of CHM-273S to upregulate IRS2 mRNA expression. CHM-273S showed a prominent anorexigenic effect in mice with the induction of a key mechanism of leptin signaling via STAT3 in the hypothalamus as a possible effector. In the animal model of metabolic disease, CHM-273S alleviated glucose intolerance and insulin resistance, and induced phosphorylation of Akt at Ser473 and Thr308 in the hepatocytes of high-sucrose diet-fed rats. In a murine model of T2D, CHM-273S mitigated high-fat diet-induced hyperglycemia and insulin resistance and improved low-grade inflammation by diminishing serum TNFα. Mice treated with chronic CHM-273S had a significant reduction in body weight, with a lower visceral fat pad weight and narrow adipocytes. The effects of the peptide administration were comparable to those of metformin. We show the potential of CHM-273S to alleviate diet-induced metabolic alterations in rodents, substantiating its further development as a therapeutic for obesity, T2D, and other metabolic conditions.

The novel peptide LCGM-10 attenuates metabotropic glutamate receptor 5 activity and demonstrates behavioral effects in animal models

“…Here we employed computational modeling to search for peptides that interact with the NAM site of mGluR5. We focused on peptides as potential therapeutics because of their safety and tolerability profiles, which are superior to those of other small molecules ( Lau and Dunn, 2018 ; Malyshev et al, 2021 ; Mitkin et al, 2022 ). We identified four novel, previously undescribed peptides with predicted affinity to the mGluR5 NAM site based on in silico docking studies and revealed that two of them, LCGM-10 and LCGM-15, have a potential stimulating effect in zebrafish.…”