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

Author(s)

Silverio, Renata ; Barth, Robson ; Heimann, Andrea S. ; Reckziegel, Patricia ; dos Santos, Gustavo J. ; Romero-Zerbo, Silvana Y. ; Bermudez-Silva, Francisco J. ; Rafacho, Alex ; Ferro, Emer S.

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 8, p. 19-pg., 2022-04-01.

Abstract

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. (AU)

• FAPESP's process: 19/25943-1 - Intracellular peptides as modulators of thermogenesis-related metabolic pathways
• Grantee: Patrícia Reckziegel
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/04000-3 - Pharmacology of oligopeptidases and intracellular peptides
• Grantee: Emer Suavinho Ferro
• Support Opportunities: Research Projects - Thematic Grants