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The activation of immune-pineal axis by high-fat diet

Grant number: 15/04557-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2015
Effective date (End): April 30, 2019
Field of knowledge:Biological Sciences - Physiology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Regina Pekelmann Markus
Grantee:Sanseray da Silveira Cruz Machado
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/13691-1 - Immune-pineal axis: time-niology integrated to surveillance and defense, AP.TEM


The pineal gland regulates several biological rhythms and defense responses in healthy subjects by producing melatonin at nighttime. On the other hand, inflammatory mediators impair pineal melatonin synthesis. Our preliminary data presented in this project highlights that low-grade inflammation generated by diet-induced obesity model inhibits nocturnal melatonin synthesis at night and body weight gain. In addition, the recovery of circadian melatonin levels in the nocturnal drinking water protects against high-fat diet-induced weight gain. Altogether, our results suggest that pineal gland senses inflammatory mediators from high-fat feeding in order to activate the immune-pineal axis and suppress the circadian melatonin production. This project aim to investigate the time-course that HFD promotes the activation of the immune-pineal axis, reduces pineal melatonin production and activates macrophage/microglia cells and extra-pineal melatonin synthesis. This project will also investigate whether circadian melatonin synthesis is recovered after chronic exposition to HFD or after body weight loss. In addition, this project will analyze the use of melatonin or analogs as therapy in the prevention of weight gain or treatment of obesity-related metabolic syndrome, as well as determine the importance of daily melatonin rhythm as a marker for serological diagnostic complement. (AU)

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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)
DA SILVEIRA CRUZ-MACHADO, SANSERAY; GUISSONI CAMPOS, LEILA MARIA; FADINI, CINTIA CRISTINA; ANDERSON, GEORGE; MARKUS, REGINA P.; PINATO, LUCIANA. Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances. Journal of Pineal Research, v. 70, n. 3 JAN 2021. Web of Science Citations: 3.
KOMEGAE, EVILIN N.; FONSECA, MONIQUE T.; CRUZ-MACHADO, SANSERAY DA SILVEIRA; TURATO, WALTER M.; FILGUEIRAS, LUCIANO R.; MARKUS, REGINA P.; STEINER, ALEXANDRE A. Site-Specific Reprogramming of Macrophage Responsiveness to Bacterial Lipopolysaccharide in Obesity. FRONTIERS IN IMMUNOLOGY, v. 10, JUN 28 2019. Web of Science Citations: 0.
MARKUS, REGINA P.; FERNANDES, PEDRO A.; KINKER, GABRIELA S.; CRUZ-MACHADO, SANSERAY DA SILVEIRA; MARCOLA, MARINA. Immune-pineal axis - acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes. British Journal of Pharmacology, v. 175, n. 16, SI, p. 3239-3250, AUG 2018. Web of Science Citations: 12.
DE ASSIS, L. V. M.; MORAES, M. N.; DA SILVEIRA CRUZ-MACHADO, S.; CASTRUCCI, A. M. L. The effect of white light on normal and malignant murine melanocytes: A link between opsins, clock genes, and melanogenesis. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1863, n. 6, A, p. 1119-1133, JUN 2016. Web of Science Citations: 19.

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