Exploring the role of adipose tissue-derived circulating miRNAs in the beneficial effects of exercise training

• Grant number: 17/07975-8
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2017
• End date: August 31, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Marcelo Alves da Silva Mori
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Alessandro dos Santos Farias ; Cesar Renato Sartori ; Claudio Cesar Zoppi ; Daniel Martins-de-Souza ; Rafael Evangelista Pedro ; Sidney Barnabé Peres

Abstract

The incidence of metabolic diseases reached global epidemics and prescription of exercise is among the safest and most efficacious alternatives to overcome this trend. Although effective, exercise training demands discipline and may not work for all individuals on the long term. Therefore, new adjuvant strategies or mimetic interventions may help patients to control their dysfunctional metabolism. Our group has found that increased miRNA biogenesis in adipose tissue is a common feature of both dietary restriction and exercise training, overcoming down-regulation that occurs with aging, obesity and lipodystrophy. Moreover, exclusive loss of miRNA biogenesis in adipocytes (i.e. the AdicerKO mice) leads to adipose tissue insulin resistance, and impaired oxidative metabolism and inflammation. Importantly, these mice also exhibit non-adipose phenotypes such as impaired muscle metabolism, whole body insulin resistance and increased risk of premature death. AdicerKO mice are also partially resistant to the beneficial effects of dietary restriction and exercise training. Recently we reported that the adipose tissue is the main source of circulating miRNAs in mice and possibly humans. Taken together, these observations lead us to hypothesize that adipose tissue derived circulating miRNAs (atdc-miRNAs) control part of the systemic effects of dietary restriction and exercise training and therefore participate in the pathophysiology of metabolic diseases. Here we will focus on the role of exercise in controlling atdc-miRNAs in mice and humans. We will test whether exercise training can reverse the metabolic complications of individuals with acquired lipodystrophy and if this is associated with changes in atdc-miRNAs. Moreover, we will define if and how atdc-miRNAs control the onset of immunosenescence in lipodystrophic humans and mice, given that impaired immune system is a hallmark of metabolic diseases. We thus aim to find atdc-miRNAs that mediate the crosstalk between the adipose tissue and the immune system to control the onset of metabolic diseases at a systemic level, thus contributing to the understanding of novel endocrine mechanisms. (AU)

Scientific publications

(10)

(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)

LUDWIG, RAISSA G.; ROCHA, ANDREA L.; MORI, MARCELO A.. Circulating molecules that control brown/beige adipocyte differentiation and thermogenic capacity. Cell Biology International, v. 42, n. 6, SI, p. 701-710, JUN 2018. (16/12294-7, 15/01316-7, 17/01184-9, 17/07975-8, 15/20822-0)

SALES, VICENCIA M.; GONCALVES-ZILLO, THAIS; CASTOLDI, ANGELA; BURGOS, MARINA; BRANQUINHO, JESSICA; BATISTA, CAROLINA; OLIVEIRA, VALERIA; SILVA, ELTON; CASTRO, CHARLLES H. M.; CAMARA, NIELS; et al. Kinin B-1 Receptor Acts in Adipose Tissue to Control Fat Distribution in a Cell-Nonautonomous Manner. Diabetes, v. 68, n. 8, p. 1614-1623, AUG 2019. (17/07975-8, 17/01184-9, 14/27198-8)

BRANDAO, BRUNA B.; MADSEN, SOREN; RABIEE, ATEFEH; OLIVERIO, MATTEO; RUIZ, GABRIEL P.; FERRUCCI, DANILO L.; BRANQUINHO, JESSICA L.; RAZOLLI, DANIELA; PINTO, SILAS; NIELSEN, THOMAS S.; et al. Dynamic changes in DICER levels in adipose tissue control metabolic adaptations to exercise. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 117, n. 38, p. 23932-23941, SEP 22 2020. (17/03423-0, 15/01316-7, 17/04377-2, 12/06238-6, 15/03292-8, 17/01184-9, 12/04079-8, 18/21635-8, 17/07975-8)

RUIZ, GABRIEL PALERMO; CAMARA, HENRIQUE; FAZOLINI, NARAYANA P. B.; MORI, MARCELO A.. Extracellular miRNAs in redox signaling: Health, disease and potential therapies. Free Radical Biology and Medicine, v. 173, p. 170-187, SEP 2021. (17/01339-2, 17/01184-9, 18/21635-8, 17/23920-9, 17/07975-8)

LUDWIG, RAISSA G.; ROCHA, ANDREA L.; MORI, MARCELO A.. Circulating molecules that control brown/beige adipocyte differentiation and thermogenic capacity. Cell Biology International, v. 42, n. 6, p. 10-pg., 2018-06-01. (17/01184-9, 17/07975-8, 15/20822-0, 16/12294-7, 15/01316-7)

GUERRA, BEATRIZ A.; BRANDAO, BRUNA B.; PINTO, SILAS S.; SALGUEIRO, WILLIAN G.; DE-SOUZA, EVANDRO A.; REIS, FELIPE C. G.; BATISTA, THIAGO M.; CAVALCANTE-SILVA, VANESSA; D'ALMEIDA, VANIA; CASTILHO, BEATRIZ A.; et al. Dietary sulfur amino acid restriction upregulates DICER to confer beneficial effects. MOLECULAR METABOLISM, v. 29, p. 124-135, NOV 2019. (15/03292-8, 17/22057-5, 10/52557-0, 16/02207-0, 17/01184-9, 15/01316-7, 15/19530-5, 12/07259-7, 17/07975-8)

MORI, MARCELO A.; LUDWIG, RAISSA G.; GARCIA-MARTIN, RUBEN; BRANDAO, BRUNA B.; KAHN, C. RONALD. Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease. Cell Metabolism, v. 30, n. 4, p. 656-673, OCT 1 2019. (17/23920-9, 17/07975-8, 17/01184-9)

ROCHA, ANDREA LIVIA; DE LIMA, TANES IMAMURA; DE SOUZA, GERSON PROFETA; CORREA, RENAN OLIVEIRA; FERRUCCI, DANILO LOPES; RODRIGUES, BRUNO; LOPES-RAMOS, CAMILA; NILSSON, DANIEL; KNITTEL, THIAGO LEITE; CASTRO, POLLYANA RIBEIRO; et al. Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression. SCIENCE ADVANCES, v. 6, n. 49, DEC 2020. (10/52557-0, 17/01184-9, 18/15313-8, 16/23142-3, 17/07975-8, 16/24163-4, 15/01316-7, 16/12294-7)

FERREIRA, JULIO C. B.; MORI, MARCELO A.; GROSS, ERIC R.. Mitochondrial Bioenergetics and Quality Control Mechanisms in Health and Disease. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2019, p. 3-pg., 2019-01-20. (15/20783-5, 17/07975-8, 17/01184-9, 12/05765-2, 18/18627-3, 17/16694-2)

MORI, MARCELO A.. Editorial: Non-Coding RNAs: Entwining Metabolism and Aging. FRONTIERS IN ENDOCRINOLOGY, v. 9, p. 2-pg., 2018-03-19. (17/07975-8, 17/01184-9)