Intracellular peptides as modulators of thermogenesis-related metabolic pathways

• Grant number: 19/25943-1
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: November 01, 2020
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Patrícia Reckziegel
• Grantee: Patrícia Reckziegel
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Emer Suavinho Ferro ; Gustavo José da Silva Pereira ; William Tadeu Lara Festuccia
• Associated research grant(s): 24/02202-4 - Identification of intracellular peptides and their relationship with thermogenesis: An omics approach, AP.R
• Associated scholarship(s): 23/02579-8 - Can peptides derived from the UCP1 protein modulate parameters related to thermogenesis in white and brown adipocytes?, BP.IC; 21/03717-0 - Characterization of intracellular peptides from adipose tissues of animals with brown adipose tissue activation and browning due cold-exposure and PPARg-agonist treatment, BP.DD; 21/02953-1 - Intracellular peptides as modulators of thermogenesis-related metabolic pathways, BP.JP

Abstract

Brown adipose tissue (BAT) is thermogenic due to the presence of mitochondrial-rich adipocytes with a high amount of mitochondrial uncoupling protein 1 (UCP1), a protein that dissipates energy from ATP synthesis for heat production. Under certain stimulus, white adipose tissue (WAT) cells may exhibit brown adipocyte characteristics in a process called browning. BAT activation and browning have been shown to be promising in the treatment of obesity and associated diseases, largely due to increased energy metabolism, glucose and triglyceride uptake. Intracellular peptides have been shown to be modulators of various pathways related to energy metabolism, they are probably differently present in BAT and WAT tissues, as well as during BAT activation and browning processes, exerting modulatory effects. Given this, the present study aims to investigate the in vitro and in vivo biological effects of intracellular peptides identified in BAT and WAT samples from mice under thermogenic stimulation. For this, intracellular peptides will be identified from adipose tissues of mice exposed to thermoneutral conditions (30ºC) or cold (4°C) and treated with vehicle or pioglitazone (PPAR³ agonist) for 15 days. Histological, gene and protein expression analyzes should prove BAT activation and browning in these animals. Peptidomic analysis will innovatively identify the intracellular peptide content of BAT and inguinal WAT samples, and the peptides altered in the thermogenic process. Some of these peptides will be selected and synthesized for in vitro studies in primary culture of brown and white adipocytes. Peptides that will positively modulate thermogenic-related parameters in vitro will be investigated in obese mice and a detailed metabolic analysis will be performed with these obese animals. Thus, we intended to characterize the role of intracellular peptides in BAT versus WAT, to verify the main points where intracellular peptides can modulate thermogenesis, and to identify new biological peptides with potential for the treatment of obesity and associated diseases. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

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.. 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, v. 23, n. 8, p. 19-pg., 2022-04-01. (19/25943-1, 16/04000-3)

CASTRO, ERIQUE; VIEIRA, THAYNA S.; OLIVEIRA, TIAGO E.; ORTIZ-SILVA, MILENE; ANDRADE, MAYNARA L.; TOMAZELLI, CAROLINE A.; PEIXOTO, ALBERT S.; SOBRINHO, CLEYTON R.; MORENO, MAYARA F.; GILIO, GUSTAVO R.; et al. Adipocyte-specific mTORC2 deficiency impairs BAT and iWAT thermogenic capacity without affecting glucose uptake and energy expenditure in cold-acclimated mice. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 321, n. 5, p. E592-E605, NOV 2021. (16/23169-9, 19/25943-1, 17/23040-9, 15/13508-8, 17/17582-3, 18/03418-0, 17/17403-1, 17/12260-8, 19/01763-4, 19/17660-0, 15/19530-5, 20/09399-7, 19/04271-5, 12/25317-4)

RECKZIEGEL, PATRICIA; PETROVIC, NATASA; CANNON, BARBARA; NEDERGAARD, JAN. Perfluorooctanoate (PFOA) cell-autonomously promotes thermogenic and adipogenic differentiation of brown and white adipocytes. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, v. 271, p. 12-pg., 2024-01-17. (19/25943-1, 17/08850-4)

CAPRIOLI, BRUNA; EICHLER, ROSANGELA A. S.; SILVA, RENEE N. O.; MARTUCCI, LUIZ FELIPE; RECKZIEGEL, PATRICIA; FERRO, EMER S.. Neurolysin Knockout Mice in a Diet-Induced Obesity Model. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 20, p. 22-pg., 2023-10-01. (16/04000-3, 19/25943-1)

GALVAO VALDIVIA, LUIS FELIPE; CASTRO, ERIQUE; DOS SANTOS EICHLER, ROSANGELA APARECIDA; MORENO, MAYARA FRANZOI; DE SOUSA, ERICA; RODRIGUES JARDIM, GIOVANNA FREITAS; PEIXOTO, ALBERT SOUZA; MORAES, MARIA NATHALIA; DE LAURO CASTRUCCI, ANA MARIA; NEDERGAARD, JAN; et al. Cold acclimation and pioglitazone combined increase thermogenic capacity of brown and white adipose tissues but this does not translate into higher energy expenditure in mice. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 324, n. 4, p. 16-pg., 2023-04-01. (17/26651-9, 21/02953-1, 19/01763-4, 20/04159-8, 18/14728-0, 21/03717-0, 17/24615-5, 19/25943-1)