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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Brain STAT5 Modulates Long-Term Metabolic and Epigenetic Changes Induced by Pregnancy and Lactation in Female Mice

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Teixeira, Pryscila D. S. [1] ; Ramos-Lobo, Angela M. [1] ; Furigo, Isadora C. [1] ; Donato, Jr., Jose [1]
Total Authors: 4
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508000 Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Endocrinology; v. 160, n. 12, p. 2903-2917, DEC 2019.
Web of Science Citations: 1

Several metabolic and behavioral adaptations that emerge during pregnancy remain present after weaning. Thus, reproductive experience causes long-lasting metabolic programming, particularly in the brain. However, the isolate effects of pregnancy or lactation and the molecular mechanisms involved in these long-term modifications are currently unknown. In the current study, we investigated the role of brain signal transducer and activator of transcription-5 (STAT5), a key transcription factor recruited by hormones highly secreted during gestation or lactation, for the long-term adaptations induced by reproductive experience. In control mice, pregnancy followed by lactation led to increased body adiposity and reduced ambulatory activity later in life. Additionally, pregnancy+ lactation induced long-term epigenetic modifications in the brain: we observed upregulation in hypothalamic expression of histone deacetylases and reduced numbers of neurons with histone H3 acetylation in the paraventricular, arcuate, and ventromedial nuclei. Remarkably, brain-specific STAT5 ablation prevented all metabolic and epigenetic changes observed in reproductively experienced control female mice. Nonetheless, brain-specific STAT5 knockout (KO) mice that had the experience of pregnancy but did not lactate showed increased body weight and reduced energy expenditure later in life, whereas pregnancy KO and pregnancy+ lactation KO mice exhibited improved insulin sensitivity compared with virgin KO mice. In summary, lactation is necessary for the long-lasting metabolic effects observed in reproductively experienced female mice. In addition, epigenetic mechanisms involving histone acetylation in neuronal populations related to energy balance regulation are possibly associated with these long-term consequences. Finally, our findings highlighted the key role played by brain STAT5 signaling for the chronic metabolic and epigenetic changes induced by pregnancy and lactation. (AU)

FAPESP's process: 14/11752-6 - Study of leptin functions during intrauterine and childhood stages in mice
Grantee:Angela Maria Ramos Lobo
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/02983-2 - The role of growth hormone in the brain: relevance for neural functions and in disease
Grantee:Jose Donato Junior
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/10992-6 - Investigation of metabolic programming through different approaches
Grantee:Jose Donato Junior
Support type: Regular Research Grants