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

Mitkin, N.A.; Pavshintcev, V.V.; Sukhanova, I.A.; Doronin, I.I.; Babkin, G.A.; Sadagurski, M.; Malyshev, A.V.

Авторы: Mitkin Nikita A., Pavshintcev Vsevolod V., Sukhanova Iuliia A., Doronin Igor I., Babkin Gennady A., Sadagurski Marianna, Malyshev Anton V.
Журнал: Pharmaceutics
Том: 14
Номер: 10
Год издания: 2022
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 2088
DOI: 10.3390/pharmaceutics14102088
Аннотация: 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.
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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 Modelsстатья Исследовательская статья

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