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Analysis of the mechanisms involved in GPR40-induced hypothalamic neuroplasticity: potential role in adult neurogenesis

Grant number: 19/10961-4
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2019
Effective date (End): October 18, 2020
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Licio Augusto Velloso
Grantee:Daiane Fátima Engel
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


There is extensive experimental evidence that high fat diet-induced obesity is accompanied by functional and structural alterations in the hypothalamus, the central structure involved in the control of caloric intake and energy homeostasis. Depending on time and magnitude of hypothalamic damage, key neurons involved in the regulation of food intake and energy expenditure can undergo apoptosis. Studies have shown that under physiological conditions, postnatal neurogenesis contributes to the maintenance of the number of neurons in the adult hypothalamus, influencing the energy homeostasis control. Previous studies have shown that polyunsaturated fatty acids induce an increase in the number of proliferating cells and mature neurons in the hypothalamus which seems to be mediated by activation of the GPR40 receptor (a free fatty acid receptor). Therefore, we hypothesized that GPR40 might play an important role in regulating the adult hypothalamic neuroplasticity involved in energy homeostasis control. Our preliminary data showed that the specific GPR40 activation induces cell proliferation of adult neural progenitors in the hypothalamus. Therefore, we hypothesized that GPR40 represents a good target to modulate adult hypothalamic neurogenesis and energy homeostasis control. Thus, we intend to characterize the role of GPR40 in determining cell fate of hypothalamic newborn neurons as well as, the mechanism involved in the neurogenic potential of its activation, and how this process can be altered in obesity.

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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)
ENGEL, DAIANE F.; BOBBO, VANESSA C. D.; SOLON, CARINA S.; NOGUEIRA, GUILHERME A.; MOURA-ASSIS, ALEXANDRE; MENDES, NATALIA F.; ZANESCO, ARIANE M.; PAPANGELIS, ATHANASIOS; ULVEN, TROND; VELLOSO, LICIO A.. Activation of GPR40 induces hypothalamic neurogenesis through p38-and BDNF-dependent mechanisms. SCIENTIFIC REPORTS, v. 10, n. 1, . (13/07607-8, 14/50938-8, 18/01360-4, 19/10961-4)

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