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Involvment of molecular factors in metabolic changes during pregnancy: role of SOCS3

Grant number: 12/15517-6
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2012
Effective date (End): August 31, 2015
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Jose Donato Junior
Grantee:Thais Tessari Zampieri
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:10/18086-0 - Molecular basis of leptin resistance, AP.JP


About half of Brazilian adults are obese or overweight, and excess weight gain during pregnancy is one of the most important risk factors for the development of obesity in women. In addition to excessive weight gain during pregnancy, gestational diabetes is another metabolic problem often faced by pregnant women. Despite recent advances in understanding the physiological components that regulate energy balance, little is known about the molecular mechanisms involved in fat deposition and insulin resistance during pregnancy. It is known that pregnant women have leptin resistance. In addition, some studies have shown that expression of hypothalamic proteins known as cytokine suppressive signal (SOCS) is increased in pregnant women, in particular SOCS3. Among other effects, increased SOCS3 expression in the hypothalamus inhibits intracellular signaling induced by insulin and leptin. However, the possible involvement of SOCS3 in the etiology of leptin resistance caused by pregnancy has not yet been investigated. Thus, this project aims to generate and validate a model of genetically engineered mouse that has SOCS3 gene inactivation exclusively in cells that express the leptin receptor. Subsequently, we will investigate the role of SOCS3 in the etiology of leptin resistance observed during pregnancy. Accordingly, females with conditional deletion of SOCS3 in cells that express the leptin receptor will be mated and changes in body weight, food intake, adiposity, glycemic control, sensitivity to leptin, insulin resistance and gene expression will be evaluated throughout pregnancy. Thus, this project has the potential to reveal the molecular mechanisms involved in metabolic disorders more common during pregnancy (weight gain and insulin resistance). Furthermore, this knowledge can contribute to understanding the pathophysiology of obesity and type 2 diabetes mellitus.

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Scientific publications (14)
(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)
PEDROSO, JOAO A. B.; DA SILVA, IVSON B.; ZAMPIERI, THAIS T.; TOTOLA, LEONARDO T.; MOREIRA, THIAGO S.; TANIGUTI, ANA P. T.; DINIZ, GABRIELA P.; BARRETO-CHAVES, MARIA LUIZA M.; DONATO, JOSE, JR.. SOCS3 Ablation in Leptin Receptor-Expressing Cells Causes Autonomic and Cardiac Dysfunctions in Middle-Aged Mice despite Improving Energy and Glucose Metabolism. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 12, p. 19-pg., . (12/15517-6, 11/12893-4, 10/18086-0, 13/04703-6, 13/25032-2)
FLORES, RAFAEL APPEL; STEINBACH, RENATA; PEDROSO, JOAO A. B.; METZGER, MARTIN; DONATO, JR., JOSE; PASCHOALINI, MARTA APARECIDA. Injections of the alpha-2 adrenoceptor agonist clonidine into the dorsal raphe nucleus increases food intake in satiated rats. Neuropharmacology, v. 182, . (17/16473-6, 17/02983-2, 12/15517-6)
FURIGO, ISADORA C.; SUZUKI, MIRIAM F.; OLIVEIRA, JOAO E.; RAMOS-LOBO, ANGELA M.; TEIXEIRA, PRYSCILA D. S.; PEDROSO, JOAO A.; DE ALENCAR, AMANDA; ZAMPIERI, THAIS T.; BUONFIGLIO, DANIELLA C.; QUARESMA, PAULA G. F.; et al. Suppression of Prolactin Secretion Partially Explains the Antidiabetic Effect of Bromocriptine in ob/ob Mice. Endocrinology, v. 160, n. 1, p. 193-204, . (13/25032-2, 14/11752-6, 15/10992-6, 12/15517-6, 13/21722-4, 17/25281-3, 12/24345-4)
ZAMPIERI, THAIS TESSARI; OLIVEIRA DA SILVA, TIAGO EUGENIO; ROMEU, DEBORAH DE PAULA; TORRAO, ANDREA DA SILVA; DONATO, JR., JOSE. SOCS3 expression within leptin receptor-expressing cells regulates food intake and leptin sensitivity but does not affect weight gain in pregnant mice consuming a high-fat diet. Physiology & Behavior, v. 157, p. 109-115, . (12/15517-6, 10/18086-0, 14/06372-0)
BUONFIGLIO, DANIELLA C.; RAMOS-LOBO, ANGELA M.; FREITAS, VANESSA M.; ZAMPIERI, THAIS T.; NAGAISHI, VANESSA S.; MAGALHAES, MAGNA; CIPOLLA-NETO, JOSE; CELLA, NATHALIE; DONATO, JR., JOSE. Obesity impairs lactation performance in mice by inducing prolactin resistance. SCIENTIFIC REPORTS, v. 6, . (10/18086-0, 13/16374-7, 14/11752-6, 15/10992-6, 12/15517-6, 10/07699-1)
DA SILVA, REGINA P.; ZAMPIERI, THAIS T.; PEDROSO, JOAO A. B.; NAGAISHI, VANESSA S.; RAMOS-LOBO, ANGELA M.; FURIGO, ISADORA C.; CAMARA, NIELS O.; FRAZAO, RENATA; DONATO, JR., JOSE. Leptin Resistance Is Not the Primary Cause of Weight Gain Associated With Reduced Sex Hormone Levels in Female Mice. Endocrinology, v. 155, n. 11, p. 4226-4236, . (13/00801-3, 10/18086-0, 12/12202-4, 13/16374-7, 12/02270-2, 12/15517-6, 13/21722-4)
PEDROSO, JOAO A. B.; ZAMPIERI, THAIS T.; DONATO, JR., JOSE. Reviewing the Effects of l-Leucine Supplementation in the Regulation of Food Intake, Energy Balance, and Glucose Homeostasis. NUTRIENTS, v. 7, n. 5, p. 3914-3937, . (13/25032-2, 12/15517-6, 10/18086-0)
NAGAISHI, V. S.; CARDINALI, L. I.; ZAMPIERI, T. T.; FURIGO, I. C.; METZGER, M.; DONATO, JR., J.. POSSIBLE CROSSTALK BETWEEN LEPTIN AND PROLACTIN DURING PREGNANCY. Neuroscience, v. 259, p. 71-83, . (12/15517-6, 12/02388-3, 10/18086-0, 13/16374-7)
RAMOS-LOBO, ANGELA M.; FURIGO, ISADORA C.; TEIXEIRA, PRYSCILA D. S.; ZAMPIERI, THAIS T.; WASINSKI, FREDERICK; BUONFIGLIO, DANIELLA C.; DONATO, JR., JOSE. Maternal metabolic adaptations are necessary for normal offspring growth and brain development. PHYSIOLOGICAL REPORTS, v. 6, n. 5, . (16/20897-3, 12/15517-6, 15/10992-6, 14/11752-6)
ZAMPIERI, THAIS T.; PEDROSO, JOAO A. B.; FURIGO, ISADORA C.; TIRAPEGUI, JULIO; DONATO, JR., JOSE. Oral Leucine Supplementation Is Sensed by the Brain but neither Reduces Food Intake nor Induces an Anorectic Pattern of Gene Expression in the Hypothalamus. PLoS One, v. 8, n. 12, . (12/15517-6, 10/18086-0)
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, . (10/18086-0, 12/12202-4, 12/15517-6, 13/07908-8)
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, . (13/25032-2, 10/18086-0, 14/11752-6, 12/12202-4, 15/10992-6, 13/07908-8, 12/15517-6, 13/21722-4)
ZAMPIERI, THAIS T.; TORRES-LEAL, FRANCISCO L.; CAMPANA, AMANDA B.; LIMA, FABIO B.; DONATO, JR., JOSE. L-Leucine Supplementation Worsens the Adiposity of Already Obese Rats by Promoting a Hypothalamic Pattern of Gene Expression that Favors Fat Accumulation. NUTRIENTS, v. 6, n. 4, p. 1364-1373, . (12/15517-6, 10/18086-0)
FLORES, RAFAEL APPEL; DA SILVA, EDUARDO SIMAO; RIBAS, ANDERSON SAVARIS; DAMBROS TASCHETTO, ANA PAULA; ZAMPIERI, THAIS TESSARI; DONATO, JR., JOSE; PASCHOALINI, MARTA APARECIDA. Evaluation of food intake and Fos expression in serotonergic neurons of raphe nuclei after intracerebroventricular injection of adrenaline in free-feeding rats. Brain Research, v. 1678, p. 153-163, . (12/15517-6, 10/18086-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ZAMPIERI, Thais Tessari. Molecular factors involved in the metabolic changes during pregnancy: role of SOCS3.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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