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Dicer signalling in adipocytes controlling immune function and activation of beige cells in adipose tissue

Grant number: 16/12294-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2017
Effective date (End): October 07, 2019
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Marcelo Alves da Silva Mori
Grantee:Andréa Livia Silva Rocha
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):19/10592-9 - Determining Mechanisms of miRNA-mediated Macrophage-Adipocyte Crosstalk, BE.EP.DR

Abstract

Obesity is an epidemic disease with serious health complications. The recruitment of beige adipocytes in white adipose tissue - a phenomenon called browning - results in induced thermogenesis and energy expenditure and represents a promising intervention to combat obesity and related diseases. Some immune cells in the adipose tissue (such as eosinophils and macrophages), when stimulated by cold, for example, can promote the recruitment of beige cells through anti-inflammatory mediators such as interleukins 33, 4 and 13 and the local production of catecholamine. MiRNAs have also been implicated in the regulation of adipogenesis and the maintenance of the functional identity of brown/beige adipocytes. Consistent with these observations, AdicerKO mice with adipocyte-specific knockout of Dicer - an enzyme responsible for miRNA processing - show a partial lipodystrophy phenotype and are unable to induce browning. Our preliminary data also show that the absence of Dicer in adipocytes changes the population of resident immune cells in adipose tissue of young mice, resulting in a proinflammatory milieu prior to any other pathophysiological or morphological change in adipose tissue. Thus, the purpose of this study is to investigate how the presence of Dicer and miRNAs in mature adipocytes can modulate the differentiation of beige adipocytes and if this phenomenon is associated with local inflammatory changes. First, we will analyze if the profile of cytokines and resident immune cells in subcutaneous adipose tissue of young AdicerKO mice exposed or not to chronic cold (6 ° C for 3 days) is affected in relation to the wild type mice. Moreover, we will investigate if the impaired recruitment of beige adipocytes in these animals depends on an inflammatory modulation and if mature adipocytes from AdicerKO animals induce polarization/activation of M1 macrophages in vitro. Investigating how Dicer in adipocytes controls the remodeling of resident immune cells in adipose tissue and impacts on the development of beige adipocytes can reveal important mechanisms to prevent obesity and its deleterious consequences.

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Scientific publications
(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)
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; FERNANDES, MARIANE FONT; MARTINS, FLAVIANO DOS SANTOS; PARMIGIANI, RAPHAEL BESSA; SILVEIRA, LEONARDO REIS; CARVALHO, HERNANDES F.; AUWERX, JOHAN; VINOLO, MARCO AURELIO R.; BOUCHER, JEREMIE; MORI, MARCELO A. Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression. SCIENCE ADVANCES, v. 6, n. 49 DEC 2020. Web of Science Citations: 0.
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. Web of Science Citations: 1.

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