Central effects of growth hormone on energetic metabolism and glicemic control

• Grant number: 16/09679-4
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): November 01, 2016
• Effective date (End): December 14, 2020
• Field of knowledge: Biological Sciences - Physiology
• Principal researcher: Jose Donato Junior
• Grantee: Isadora Clivatti Furigo
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/06313-7 - Impact of maternal obesity on offspring hypothalamic neurocircuits: microRNA expression profiling of arcuate and paraventricular nuclei and associated outcomes, BE.EP.PD

Abstract

Growth Hormone (GH) is a key anabolic hormone and its action on periferic tissues is related to several biologic functions such as somatic growth, metabolism and cellular processes (cellular division and regeneration). Growth Hormone-Releasing factor (GHRH) and growth hormone-inhibiting hormone (somatostatin), as well as free-fat acids, leptin, ghrelin and neuropeptide Y are important factors that control GH releasing. Nutritional state, intense physical activity, stress and fasting are also powerful releasing factors. There is evidence, but still poorly investigated, that GH might exert effects on the Central Nervous System (CNS), possibly controlling appetite, cognition, memory, mood, sleep, neuronal protection and well-being. Recently, our group mapped in detail the presence of GH responsive cells in the mouse CNS, and identified several brain sites in which GH possibly interacts with leptin, suggesting a direct action on neurons involved in energy balance and glycemia regulation. The aim of the present study is to investigate in detail the GH function in CNS, especially on glycemic control and energetic metabolism at basal situations, as well as during situations in which GH is highly secreted (e.g., food restriction, hypoglycemia and physical activity). For this purpose, we will use mouse models with conditional deletion of GH receptor (GHR-flox mice) in the CNS (Nestin-Cre mice), ventromedial nucleus of hypothalamus and (SF1-Cre mice) or leptin receptor-expressing cells (LepR-Cre mice). (AU)

Scientific publications

(15)

(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)

FURIGO, ISADORA C.; TEIXEIRA, PRYSCILA D. S.; DE SOUZA, GABRIEL O.; COUTO, GISELE C. L.; GARCIA ROMERO, GUADALUPE; PERELLO, MARIO; FRAZAO, RENATA; ELIAS, LUCILA L.; METZGER, MARTIN; LIST, EDWARD O.; et al. Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons. NATURE COMMUNICATIONS, v. 10, FEB 8 2019. (17/21840-8, 17/05007-4, 17/16473-6, 16/09679-4, 17/04006-4, 17/02983-2)

SILVEIRA, MARINA A.; ZAMPIERI, THAIS T.; FURIGO, ISADORA C.; ABDULKADER, FERNANDO; DONATO, JR., JOSE; FRAZAO, RENATA. Acute effects of somatomammotropin hormones on neuronal components of the hypothalamic-pituitary-gonadal axis. Brain Research, v. 1714, p. 210-217, JUL 1 2019. (17/02983-2, 13/07908-8, 15/20198-5, 16/09679-4)

QUARESMA, PAULA G. F.; TEIXEIRA, PRYSCILA D. S.; FURIGO, ISADORA C.; WASINSKI, FREDERICK; COUTO, GISELE C.; FRAZAO, RENATA; LIST, EDWARD O.; KOPCHICK, JOHN J.; DONATO JR, JOSE. Growth hormone/STAT5 signaling in proopiomelanocortin neurons regulates glucoprivic hyperphagia. Molecular and Cellular Endocrinology, v. 498, DEC 1 2019. (17/21840-8, 17/25281-3, 16/09679-4, 17/04006-4, 17/02983-2, 16/20897-3)

WASINSKI, FREDERICK; PEDROSO, JOAO A. B.; DOS SANTOS, WILLIAN O.; FURIGO, ISADORA C.; GARCIA-GALIANO, DAVID; ELIAS, CAROL F.; LIST, EDWARD O.; KOPCHICK, JOHN J.; SZAWKA, RAPHAEL E.; DONATO JR, JOSE. Tyrosine Hydroxylase Neurons Regulate Growth Hormone Secretion via Short-Loop Negative Feedback. JOURNAL OF NEUROSCIENCE, v. 40, n. 22, p. 4309-4322, MAY 27 2020. (16/20897-3, 17/02983-2, 16/09679-4)

WASINSKI, FREDERICK; FURIGO, ISADORA C.; TEIXEIRA, PRYSCILA D. S.; RAMOS-LOBO, ANGELA M.; PERONI, CIBELE N.; BARTOLINI, PAOLO; LIST, EDWARD O.; KOPCHICK, JOHN J.; DONATO JR, JOSE. Growth Hormone Receptor Deletion Reduces the Density of Axonal Projections from Hypothalamic Arcuate Nucleus Neurons. Neuroscience, v. 434, p. 136-147, MAY 10 2020. (16/20897-3, 14/11752-6, 17/02983-2, 16/09679-4)

FURIGO, ISADORA C.; MELO, HELEN M.; LYRA E SILVA, NATALIA M.; RAMOS-LOBO, ANGELA M.; TEIXEIRA, PRYSCILA D. S.; BUONFIGLIO, DANIELLA C.; WASINSKI, FREDERICK; LIMA, ELIANA R.; HIGUTI, ELIZA; PERONI, CIBELE N.; et al. Brain STAT5 signaling modulates learning and memory formation. Brain Structure & Function, v. 223, n. 5, p. 2229-2241, JUN 2018. (12/02388-3, 15/10992-6, 14/11752-6, 12/24345-4, 16/09679-4, 17/02983-2, 16/20897-3)

FURIGO, ISADORA C.; DE SOUZA, GABRIEL O.; TEIXEIRA, PRYSCILA D. S.; GUADAGNINI, DIOZE; FRAZAO, RENATA; LIST, EDWARD O.; KOPCHICK, JOHN J.; PRADA, PATRICIA O.; DONATO, JR., JOSE. Growth hormone enhances the recovery of hypoglycemia via ventromedial hypothalamic neurons. FASEB JOURNAL, v. 33, n. 11, p. 11909-11924, NOV 2019. (17/02983-2, 18/20087-7, 17/18498-6, 16/09679-4)

BUENO, DEBORA; LIMA, LEANDRO B.; SOUZA, RUDIERI; GONCALVES, LUCIANO; LEITE, FERNANDA; SOUZA, STEFANI; FURIGO, ISADORA C.; DONATO, JR., JOSE; METZGER, MARTIN. Connections of the laterodorsal tegmental nucleus with the habenular-interpeduncular-raphe system. JOURNAL OF COMPARATIVE NEUROLOGY, v. 527, n. 18, p. 3046-3072, DEC 15 2019. (17/16473-6, 17/02983-2, 16/09679-4)

QUARESMA, PAULA G. F.; WASINSKI, FREDERICK; MANSANO, NAIRA S.; FURIGO, ISADORA C.; TEIXEIRA, PRYSCILA D. S.; GUSMAO, DANIELA O.; FRAZAO, RENATA; DONATO JR, JOSE. Leptin Receptor Expression in GABAergic Cells is Not Sufficient to Normalize Metabolism and Reproduction in Mice. Endocrinology, v. 162, n. 11, NOV 2021. (21/03316-5, 16/09679-4, 19/21707-1, 17/25281-3, 20/01318-8, 17/22189-9, 16/20897-3)

TEIXEIRA, PRYSCILA D. S.; COUTO, GISELE C.; FURIGO, ISADORA C.; LIST, EDWARD O.; KOPCHICK, JOHN J.; DONATO, JR., JOSE. Central growth hormone action regulates metabolism during pregnancy. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 317, n. 5, p. E925-E940, NOV 2019. (17/02983-2, 17/04006-4, 16/09679-4)

RAMOS-LOBO, ANGELA M.; TEIXEIRA, PRYSCILA D. S.; FURIGO, ISADORA C.; MELO, HELEN M.; LYRA E SILVA, NATALIA DE M.; DE FELICE, FERNANDA G.; DONATO, JR., JOSE. Long-term consequences of the absence of leptin signaling in early life. eLIFE, v. 8, JAN 29 2019. (16/09679-4, 15/10992-6, 14/11752-6)

FURIGO, ISADORA C.; TEIXEIRA, PRYSCILA D. S.; QUARESMA, PAULA G. F.; MANSANO, NAIRA S.; FRAZAO, RENATA; DONATO JR, JOSE. STAT5 ablation in AgRP neurons increases female adiposity and blunts food restriction adaptations. JOURNAL OF MOLECULAR ENDOCRINOLOGY, v. 64, n. 1, p. 13-27, JAN 2020. (17/22189-9, 17/02983-2, 17/25281-3, 16/09679-4, 17/21840-8)

BOHLEN, TABATA M.; ZAMPIERI, THAIS T.; FURIGO, ISADORA C.; TEIXEIRA, PRYSCILA D. S.; LIST, EDWARD O.; KOPCHICK, JOHN J.; DONATO, JR., JOSE; FRAZAO, RENATA. Central growth hormone signaling is not required for the timing of puberty. Journal of Endocrinology, v. 243, n. 3, p. 161-173, DEC 2019. (17/02983-2, 16/09679-4, 15/20198-5, 15/14588-5)

PEDROSO, JOAO A. B.; DOS SANTOS, LUCAS B. P.; FURIGO, ISADORA C.; SPAGNOL, ALEXANDRE R.; WASINSKI, FREDERICK; LIST, EDWARD O.; KOPCHICK, JOHN J.; DONATO JR, JOSE. Deletion of growth hormone receptor in hypothalamic neurons affects the adaptation capacity to aerobic exercise. Peptides, v. 135, JAN 2021. (17/02983-2, 16/09679-4, 16/20897-3)

DONATO, JR., JOSE; WASINSKI, FREDERICK; FURIGO, ISADORA C.; METZGER, MARTIN; FRAZAO, RENATA. Central Regulation of Metabolism by Growth Hormone. CELLS, v. 10, n. 1, JAN 2021. (20/01318-8, 16/09679-4, 19/21707-1, 16/20897-3, 17/16473-6)