Silvério, RenataBarth, RobsonHeimann, Andrea SReckziegel, PatríciaDos Santos, Gustavo JRomero-Zerbo, Silvana YBermudez-Silva, Francisco JRafacho, AlexFerro, Emer S2023-05-032023-05-032022-04-01Silvério R, Barth R, Heimann AS, Reckziegel P, Dos Santos GJ, Romero-Zerbo SY, et al. Pep19 Has a Positive Effect on Insulin Sensitivity and Ameliorates Both Hepatic and Adipose Tissue Phenotype of Diet-Induced Obese Mice. Int J Mol Sci. 2022 Apr 7;23(8):4082http://hdl.handle.net/10668/21149Peptide DIIADDEPLT (Pep19) has been previously suggested to improve metabolic parameters, without adverse central nervous system effects, in a murine model of diet-induced obesity. Here, we aimed to further evaluate whether Pep19 oral administration has anti-obesogenic effects, in a well-established high-fat diet-induced obesity model. Male Swiss mice, fed either a standard diet (SD) or high-fat diet (HFD), were orally administrated for 30 consecutive days, once a day, with saline vehicle or Pep19 (1 mg/kg). Next, several metabolic, morphological, and behavioral parameters were evaluated. Oral administration of Pep19 attenuated HFD body-weight gain, reduced in approximately 40% the absolute mass of the endocrine pancreas, and improved the relationship between circulating insulin and peripheral insulin sensitivity. Pep19 treatment of HFD-fed mice attenuated liver inflammation, hepatic fat distribution and accumulation, and lowered plasma alanine aminotransferase activity. The inguinal fat depot from the SD group treated with Pep19 showed multilocular brown-fat-like cells and increased mRNA expression of uncoupling protein 1 (UCP1), suggesting browning on inguinal white adipose cells. Morphological analysis of brown adipose tissue (BAT) from HFD mice showed the presence of larger white-like unilocular cells, compared to BAT from SD, Pep19-treated SD or HFD mice. Pep19 treatment produced no alterations in mice behavior. Oral administration of Pep19 ameliorates some metabolic traits altered by diet-induced obesity in a Swiss mice model.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/bioactive peptidesintracellular peptidesmetabolismobesityorally active peptidesoverweightAdipose tissueAdipose tissue, brownAdipose tissue, whiteAnimalsDiet, high-fatInsulin resistanceLiverMaleMiceMice, inbred C57BLMice, obeseNerve tissue proteinsObesityPhenotyperesearch article35456900open accessDieta alta en grasaFenotipoHígadoObesidadProteínas del tejido nerviosoResistencia a la InsulinaTejido adiposo10.3390/ijms230840821422-0067PMC9030859https://www.mdpi.com/1422-0067/23/8/4082/pdf?version=1649329427https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030859/pdf