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Varredura e caracterização de moléculas circulantes que afetam o gasto energético

Grant number: 17/23920-9
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2018
Effective date (End): September 30, 2022
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Marcelo Alves da Silva Mori
Grantee:Raissa Guimarães Ludwig
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics, AP.TEM

Abstract

The prevalence of obesity has been growing worldwide alongside its comorbidities. Current anti-obesity therapies appear to be poorly efficient, especially on the long-term, and are associated with significant side effects. There are two ways to lose weight: by decreasing energy intake or increasing energy expenditure. One way to increase energy expenditure in mammals is through the stimulation of brown/beige adipocytes and the increase in their function. This phenomenon correlates with high levels of UCP1 expression and activity. Some conditions capable of regulating UCP1 expression and function have already been described. Among them, there is chronic cold exposure, exercise, an enriched social environment, and cancer cachexia. These conditions act through cell autonomous mechanisms, such as by regulating transcription factors in preadipocytes or adipocytes, and cell non-autonomous mechanisms, such as by signaling through hormones and other circulating molecules. The study and understanding of the circulating molecules that act in adipose tissue to increase its brown/beige characteristics is essential for the development of more efficient and secure pharmacological strategies that could help to mitigate the global scenario of obesity. We observed, based on our preliminary results, that serum of mice subjected to dietary restriction modulates the expression of Ucp1 in vitro in mouse adipocytes derived from brown adipose tissue. This seems to be due to one or more circulating molecules present in the serum of ad libitum-fed individuals that induce UCP1 in a dose-dependent manner. These molecules are absent or very low in serum of DR-subjected individuals. Interestingly, this effect can be reproduced using serum of rats or obese humans subjected to bariatric surgery. We aim to find these circulating molecules that are likely proteins or protein-dependent molecules. This/these molecule(s) may bring insights into the development of new drugs to combat obesity.

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Scientific publications (4)
(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)
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, . (17/01339-2, 17/01184-9, 18/21635-8, 17/23920-9, 17/07975-8)
SACCON, TATIANA DANDOLINI; MOUSOVICH-NETO, FELIPPE; LUDWIG, RAISSA GUIMARAES; CARREGARI, VICTOR CORASOLLA; DOS ANJOS SOUZA, ANA BEATRIZ; DOS PASSOS, AMANDA STEPHANE CRUZ; MARTINI, MATHEUS CAVALHEIRO; BARBOSA, PRISCILLA PASCHOAL; DE SOUZA, GABRIELA FABIANO; MURARO, STEFANIE PRIMON; et al. SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner. NATURE COMMUNICATIONS, v. 13, n. 1, p. 15-pg., . (20/08716-9, 20/04558-0, 19/05155-9, 21/10373-5, 13/07607-8, 20/04919-2, 20/04746-0, 17/01184-9, 17/23920-9, 16/24163-4, 16/00194-8, 18/21635-8, 19/00098-7, 20/05040-4, 17/08264-8, 20/04579-7, 19/26119-0, 19/04726-2, 20/04583-4, 20/15959-5)
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, . (17/23920-9, 17/07975-8, 17/01184-9)
BRUNETTI, NATALIA S.; DAVANZO, GUSTAVO G.; DE MORAES, DIOGO; FERRARI, ALLAN J. R.; SOUZA, GABRIELA F.; MURARO, STEFANIE PRIMON; KNITTEL, THIAGO L.; BOLDRINI, VINICIUS O.; MONTEIRO, LAUAR B.; VIRGILIO-DA-SILVA, JOO VICTOR; et al. SARS-CoV-2 uses CD4 to infect T helper lymphocytes. eLIFE, v. 12, p. 26-pg., . (20/04558-0, 15/15626-8, 19/06459-1, 19/04726-2, 19/16116-4, 19/05155-9, 19/13552-8, 16/18031-8, 19/00098-7, 20/04583-4, 16/00194-8, 21/08354-2, 19/17007-4, 19/22398-2, 17/01184-9, 19/14465-1, 20/04579-7, 13/08293-7, 18/14933-2, 17/23920-9, 19/06372-3, 16/24163-4, 16/23328-0, 20/04919-2, 20/04746-0)

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