Adipose tissue contribution to the citokine storm of COVID 19 patients

• Grant number: 20/07765-6
• Support Opportunities: Regular Research Grants
• Duration: December 01, 2020 - January 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marilia Cerqueira Leite Seelaender
• Grantee: Marilia Cerqueira Leite Seelaender
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Hypothesis: White Adipose tissue (WAT) contributes, as a major endocrine gland, to the cytokine storm and systemic effects of the infection.Justification: i) WAT is a major component of inflammatory response in cachexia, a systemic disease in which hypoxia, inflammation and fibrosis occur in major organs. Therefore, it is possible to expect similarities, given the recent description of organ/tissue effects of Covid19 ii) WAT secretes all the major inflammatory cytokines, eicosanoids, and also, adipokines. There is no available literature on the expression of inflammatory cytokines/autacoids and adipokines in WAT of COVID19 patientsAims:1.To examine WAT morphology, immune infiltration, fibrosis and expression of inflammatory factors2. To investigate WAT intracellular (adipocyte and monocyte) NFKB and inflammasome pathways3. To study the load of WAT derived exosomes.Casuistic and experiments:a) SAMPLES: WAT (subcutaneous and visceral depots), plasmaUniversity Hospital (HU-USP): 40 patients with positive Covid-19 tests, submitted to emergency surgery; 20 patients negative for Covid19 tests, submitted to same surgeriesFaculty of Medicine-USP: Samples obtained from autopsies from patients who passed with Covid19 (20); equal number of control samplesb) Experiments:WAT:¾Histological analysis of tissue (light and electron microscopy)¾FACS scan study of infiltrating immune cells¾Multiplex assays for inflammatory cytokines, hypoxia-involved proteins, fibrosis pathways-related proteins¾Real time PCR for the same factors and microRNA analysis¾Western blot for assessment of phosphorylated proteins in the pathways of interest¾Tissue lipidomics¾Explant incubation and exosome separation and subsequent analysis (lipidomics, miRs)Plasma:¾Inflammatory/metabolic profiling: quantification of circulating markers of inflammation, cardiometabolic disease, neuropeptides, adipokines and hormones (insulin, cortisol, testosterone, oestradiol) CRP, cytokines, neuropeptides, adipokines, glucose, lactate, creatinine, insulin, cortisol ¾Plasma metabolomics/lipidomics;¾Exosome separation and load assessment (AU)

Scientific publications

(6)

(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)

GONCALVES, RENATA DE CASTRO; FREIRE, PAULA PACCIELLI; COLETTI, DARIO; SEELAENDER, MARILIA. Tumor Microenvironment Autophagic Processes and Cachexia: The Missing Link?. FRONTIERS IN ONCOLOGY, v. 10, FEB 2 2021. (20/09146-1, 12/50079-0, 20/07765-6)

MORESI, VIVIANA; RENZINI, ALESSANDRA; CAVIOLI, GIORGIA; SEELAENDER, MARILIA; COLETTI, DARIO; GIGLI, GIUSEPPE; CEDOLA, ALESSIA. Functional Nutrients to Ameliorate Neurogenic Muscle Atrophy. METABOLITES, v. 12, n. 11, p. 24-pg., 2022-11-01. (12/50079-0, 20/07765-6)

SILVA, BRUNA SPOLADOR DE ALENCAR; PEREIRA, TELMO; MINUZZI, LUCIELE GUERRA; PADILHA, CAMILA SOUZA; FIGUEIREDO, CAIQUE; OLEAN-OLIVEIRA, TIAGO; DOS SANTOS, IVETE VERA MEDEIROS; VON AH MORANO, ANA ELISA; MARCHIOTO, OSMAR; RIBEIRO, JOSE PROCOPIO JABUR; et al. Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit-COVID study. FRONTIERS IN IMMUNOLOGY, v. 14, p. 16-pg., 2023-09-11. (20/07765-6, 21/11932-8, 21/06338-0, 19/26378-6, 19/25626-6, 18/23402-0)

DE CASTRO, GABRIELA SALIM; ANDRADE, MARCIA FABIA; PINTO, FLAYDSON CLAYTON SILVA; FAIAD, JALINE ZANDONATO; SEELAENDER, MARILIA. mega-3 Fatty Acid Supplementation and Its Impact on Systemic Inflammation and Body Weight in Patients With Cancer Cachexia-A Systematic Review and Meta-Analysi. FRONTIERS IN NUTRITION, v. 8, JAN 31 2022. (12/50079-0, 20/07765-6)

SILVA PINTO, FLAYDSON CLAYTON; ANDRADE, MARCIA FABIA; GATTI DA SILVA, GUILHERME HENRIQUE; FAIAD, JALINE ZANDONATO; NORONHA BARRERE, ANA PAULA; GONCALVES, RENATA DE CASTRO; DE CASTRO, GABRIELA SALIM; SEELAENDER, MARILIA. Function Over Mass: A Meta-Analysis on the Importance of Skeletal Muscle Quality in COVID-19 Patients. FRONTIERS IN NUTRITION, v. 9, p. 11-pg., 2022-04-20. (20/07765-6, 12/50079-0)

DAS NEVES, RODRIGO XAVIER; YAMASHITA, ALEX S.; RICCARDI, DANIELA M. R.; KOHN-GAONE, JULIA; CAMARGO, RODOLFO G.; NETO, NELSON I.; CAETANO, DANIELA; GOMES, SILVIO P.; SANTOS, FELIPE H.; LIMA, JOANNA D. C. C.; et al. Cachexia causes time-dependent activation of the inflammasome in the liver. JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE, v. 14, n. 4, p. 10-pg., 2023-05-12. (20/07765-6, 12/50079-0)