Precocious puberty in childhood obesity: possible mechanisms and influence of leptin

• Grant number: 13/07908-8
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2015 - June 30, 2017
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Renata Frazão
• Grantee: Renata Frazão
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Jose Donato Junior

Abstract

The average age in which children have shown indicators of the onset of puberty, such as the thelarche or menarche, has declined over the decades. This fact is alarming because early puberty brings several negative implications. For example, early exposure to sex hormones increases the risk for developing cancers in reproductive organs. The early onset of puberty increases the incidence of social offenses in adolescence and can lead to psychosocial problems, when the child has not yet reached a cognitive age which is appropriate to deal with the changes that happen to your own body. In addition, the anticipation of puberty promotes precocious sexual initiation, increases the number of pregnant adolescents and can affect somatic growth. There are some hypotheses that try to explain the early onset of puberty today, but a well-known fact is that a large proportion of children are overweight. The excess of the body fat changes leptin circulating levels and the responsiveness to this hormone in the hypothalamus (leptin resistance). These changes, in turn, may contribute to an earlier onset of puberty. Therefore, this project aims to investigate the responsible mechanisms for inducing early onset of puberty in overweight children, with emphasis on the possible role played by the hormone leptin. We propose experiments aimed at manipulating circulating leptin levels and/or the sensitivity to this hormone through tissue-specific inactivation of Socs3 gene or in mouse models of childhood obesity. Thus, we will evaluate the progression of sexual maturation in these mice, correlating these data with information on leptin sensitivity, metabolic cues (body weight and leptin levels) and neuronal activity. In addition, we will study possible changes in the acute response to the effects induced by leptin in different sexual maturation stages in hypothalamic nuclei potentially involved in the control of puberty. Based on these data, we will perform molecular analyzes in these nuclei to identify potential genes that may explain the effects of leptin on the onset of puberty. In summary, this project has the potential to improve our understanding about the molecular mechanisms responsible for the precocious puberty nowadays. (AU)

Scientific publications

(8)

(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)

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. (15/20198-5, 16/09679-4, 17/02983-2, 13/07908-8)

DONATO, JR., JOSE; FRAZAO, RENATA. Interactions between prolactin and kisspeptin to control reproduction. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 60, n. 6, p. 587-595, NOV-DEC 2016. (15/10992-6, 13/07908-8)

SILVEIRA, MARINA AUGUSTO; FURIGO, ISADORA C.; ZAMPIERI, THAIS T.; BOHLEN, TABATA M.; DE PAULA, DANIELLA G.; FRANCI, CELSO RODRIGUES; DONATO, JR., JOSE; FRAZAO, RENATA. STAT5 signaling in kisspeptin cells regulates the timing of puberty. Molecular and Cellular Endocrinology, v. 448, n. C, p. 55-65, JUN 15 2017. (15/20198-5, 12/12202-4, 15/10992-6, 13/07908-8, 13/21722-4, 15/14588-5)

PAULA, DANIELLA G. DE; BOHLEN, TABATA M.; ZAMPIERI, THAIS TESSARI; MANSANO, NAIRA S.; VIEIRA, HENRIQUE R.; GUSMAO, DANIELA O.; WASINSKI, FREDERICK; DONATO JR, JOSE; FRAZAO, RENATA. Distinct effects of growth hormone deficiency and disruption of hypothalamic kisspeptin system on reproduction of male mice. Life Sciences, v. 285, NOV 15 2021. (20/01318-8, 16/03082-6, 21/03316-5, 16/20897-3, 15/20198-5, 13/07908-8, 15/14588-5, 17/22189-9)

ZAMPIERI, THAIS TESSARI; BOHLEN, TABATA MARIZ; SILVEIRA, MARINA AUGUSTO; LANA, LARISSA CAMPISTA; DE PAULA, DANIELLA G.; DONATO, JOSE; FRAZAO, RENATA. Postnatal Overnutrition Induces Changes in Synaptic Transmission to Leptin Receptor-Expressing Neurons in the Arcuate Nucleus of Female Mice. NUTRIENTS, v. 12, n. 8, AUG 2020. (16/03082-6, 17/02983-2, 13/07908-8, 15/14588-5, 15/20198-5)

PEDROSO, JOAO A. B.; SILVEIRA, MARINA A.; LIMA, LEANDRO B.; FURIGO, ISADORA C.; ZAMPIERI, THAIS T.; RAMOS-LOBO, ANGELA M.; BUONFIGLIO, DANIELLA C.; TEIXEIRA, PRYSCILA D. S.; FRAZAO, RENATA; DONATO, JR., JOSE. Changes in Leptin Signaling by SOCS3 Modulate Fasting-Induced Hyperphagia and Weight Regain in Mice. Endocrinology, v. 157, n. 10, p. 3901-3914, OCT 2016. (13/25032-2, 10/18086-0, 14/11752-6, 12/12202-4, 15/10992-6, 13/07908-8, 12/15517-6, 13/21722-4)

BOHLEN, TABATA M.; SILVEIRA, MARINA A.; ZAMPIERI, THAIS T.; FRAZAO, RENATA; DONATO, JR., JOSE. Fatness rather than leptin sensitivity determines the timing of puberty in female mice. Molecular and Cellular Endocrinology, v. 423, n. C, p. 11-21, MAR 5 2016. (10/18086-0, 12/12202-4, 12/15517-6, 13/07908-8)

FURIGO, ISADORA C.; RAMOS-LOBO, ANGELA M.; FRAZAO, RENATA; DONATO, JR., J.. Brain STAT5 signaling and behavioral control. Molecular and Cellular Endocrinology, v. 438, n. C, p. 70-76, DEC 15 2016. (14/11752-6, 12/12202-4, 10/18086-0, 15/10992-6, 13/07908-8, 13/21722-4)