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Article

Pep19 Has a Positive Effect on Insulin Sensitivity and Ameliorates Both Hepatic and Adipose Tissue Phenotype of Diet-Induced Obese Mice

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Graduate Program in Pharmacology, Federal University of Santa Catarina (UFSC), Florianópolis 88040-900, Brazil
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Laboratory of Investigation in Chronic Diseases, Department of Physiological Sciences, Federal University of Santa Catarina (UFSC), Florianópolis 88040-900, Brazil
3
Multicenter Graduate Program in Physiological Sciences, Federal University of Santa Catarina (UFSC), Florianópolis 88040-900, Brazil
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Proteimax BioTechnology Israel LTD, 4 Duvdevan Street, Pardes Hana, Haifa 3708973, Israel
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Department of Pharmacology, Biomedical Science Institute, University of São Paulo (USP), São Paulo 05508-000, Brazil
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Instituto de Investigación Biomédica de Málaga-IBIMA, UGC Endocrinología y Nutrición Hospital Regional Universitario de Málaga, Universidad de Málaga, 29009 Málaga, Spain
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Biomedical Research Center for Diabetes and Associated Metabolic Diseases (CIBERDEM), 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Ross Bathgate
Int. J. Mol. Sci. 2022, 23(8), 4082; https://doi.org/10.3390/ijms23084082
Received: 8 March 2022 / Revised: 29 March 2022 / Accepted: 1 April 2022 / Published: 7 April 2022
(This article belongs to the Special Issue Peptides and Their Synthetic Analogs in Medicine and Biotechnology)
Peptide 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. View Full-Text
Keywords: bioactive peptides; orally active peptides; intracellular peptides; overweight; obesity; metabolism bioactive peptides; orally active peptides; intracellular peptides; overweight; obesity; metabolism
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MDPI and ACS Style

Silvério, R.; Barth, R.; Heimann, A.S.; Reckziegel, P.; dos Santos, G.J.; Romero-Zerbo, S.Y.; Bermúdez-Silva, F.J.; Rafacho, A.; Ferro, E.S. 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, 23, 4082. https://doi.org/10.3390/ijms23084082

AMA Style

Silvério R, Barth R, Heimann AS, Reckziegel P, dos Santos GJ, Romero-Zerbo SY, Bermúdez-Silva FJ, Rafacho A, Ferro ES. Pep19 Has a Positive Effect on Insulin Sensitivity and Ameliorates Both Hepatic and Adipose Tissue Phenotype of Diet-Induced Obese Mice. International Journal of Molecular Sciences. 2022; 23(8):4082. https://doi.org/10.3390/ijms23084082

Chicago/Turabian Style

Silvério, Renata, Robson Barth, Andrea S. Heimann, Patrícia Reckziegel, Gustavo J. dos Santos, Silvana Y. Romero-Zerbo, Francisco J. Bermúdez-Silva, Alex Rafacho, and Emer S. Ferro. 2022. "Pep19 Has a Positive Effect on Insulin Sensitivity and Ameliorates Both Hepatic and Adipose Tissue Phenotype of Diet-Induced Obese Mice" International Journal of Molecular Sciences 23, no. 8: 4082. https://doi.org/10.3390/ijms23084082

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