Obesity impairs lactation performance in mice by inducing prolactin resistance

Autor(es)

Buonfiglio, Daniella C. ^[1] ; Ramos-Lobo, Angela M. ^[1] ; Freitas, Vanessa M. ^[2] ; Zampieri, Thais T. ^[1] ; Nagaishi, Vanessa S. ^[1] ; Magalhaes, Magna ^[2] ; Cipolla-Neto, Jose ^[1] ; Cella, Nathalie ^[2] ; Donato, Jr., Jose ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 6, MAR 1 2016.
• Citações Web of Science: 12

Resumo

Obesity reduces breastfeeding success and lactation performance in women. However, the mechanisms involved are not entirely understood. In the present study, female C57BL/6 mice were chronically exposed to a high-fat diet to induce obesity and subsequently exhibited impaired offspring viability (only 15% survival rate), milk production (33% reduction), mammopoiesis (one-third of the glandular area compared to control animals) and postpartum maternal behaviors (higher latency to retrieving and grouping the pups). Reproductive experience attenuated these defects. Diet-induced obese mice exhibited high basal pSTAT5 levels in the mammary tissue and hypothalamus, and an acute prolactin stimulus was unable to further increase pSTAT5 levels above basal levels. In contrast, genetically obese leptin-deficient females showed normal prolactin responsiveness. Additionally, we identified the expression of leptin receptors specifically in basal/myoepithelial cells of the mouse mammary gland. Finally, high-fat diet females exhibited altered mRNA levels of ERBB4 and NRG1, suggesting that obesity may involve disturbances to mammary gland paracrine circuits that are critical in the control of luminal progenitor function and lactation. In summary, our findings indicate that high leptin levels are a possible cause of the peripheral and central prolactin resistance observed in obese mice which leads to impaired lactation performance. (AU)

• Processo FAPESP: 10/18086-0 - Bases moleculares da resistência à leptina
• Beneficiário: Jose Donato Junior
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/16374-7 - Interação entre leptina e prolactina no encéfalo: possível mecanismo de alterações metabólicas na gravidez
• Beneficiário: Vanessa Sayuri Nagaishi
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/11752-6 - Estudo das funções da leptina durante o período intrauterino e infância no camundongo
• Beneficiário: Angela Maria Ramos Lobo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/10992-6 - Estudo da programação metabólica por meio de diferentes abordagens
• Beneficiário: Jose Donato Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/15517-6 - Fatores moleculares envolvidos nas alterações metabólicas durante a gestação: papel do SOCS3
• Beneficiário: Thais Tessari Zampieri
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/07699-1 - Protease ADAMTS-1 influenciando o comportamento e o microambiente do câncer de mama
• Beneficiário: Vanessa Morais Freitas
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores