{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:14:08Z","timestamp":1760231648734,"version":"build-2065373602"},"reference-count":97,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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 TNF\u03b1. 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics14102088","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T01:21:07Z","timestamp":1665364867000},"page":"2088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["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"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-9250","authenticated-orcid":false,"given":"Nikita A.","family":"Mitkin","sequence":"first","affiliation":[{"name":"Metabico Inc., Newton, MA 02460, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vsevolod V.","family":"Pavshintcev","sequence":"additional","affiliation":[{"name":"Metabico Inc., Newton, MA 02460, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9520-6698","authenticated-orcid":false,"given":"Iuliia A.","family":"Sukhanova","sequence":"additional","affiliation":[{"name":"Metabico Inc., Newton, MA 02460, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor I.","family":"Doronin","sequence":"additional","affiliation":[{"name":"Metabico Inc., Newton, MA 02460, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gennady A.","family":"Babkin","sequence":"additional","affiliation":[{"name":"Metabico Inc., Newton, MA 02460, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8203-4612","authenticated-orcid":false,"given":"Marianna","family":"Sadagurski","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Integrative Biosciences Center (IBio), Wayne State University, Detroit, MI 48202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton V.","family":"Malyshev","sequence":"additional","affiliation":[{"name":"Metabico Inc., Newton, MA 02460, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1471-0307.2006.00250.x","article-title":"Bioactive peptides and lactic fermentations","volume":"59","author":"Fitzgerald","year":"2006","journal-title":"Int. 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