RESUMO
The pituitary functions as a master endocrine gland that secretes hormones critical for regulation of a wide variety of physiological processes including reproduction, growth, metabolism and stress responses. The distinct hormone-producing cell lineages within the pituitary display remarkable levels of cell plasticity that allow remodeling of the relative proportions of each hormone-producing cell population to meet organismal demands. The molecular mechanisms governing pituitary cell plasticity have not been fully elucidated. Our recent studies have implicated a role for the Musashi family of sequence-specific mRNA binding proteins in the control of pituitary hormone production, pituitary responses to hypothalamic stimulation and modulation of pituitary transcription factor expression in response to leptin signaling. To date, these actions of Musashi in the pituitary appear to be mediated through translational repression of the target mRNAs. Here, we report Musashi1 directs the translational activation, rather than repression, of the Prop1, Gata2 and Nr5a1 mRNAs which encode key pituitary lineage specification factors. We observe that Musashi1 further directs the translational activation of the mRNA encoding the glycolipid Neuronatin (Nnat) as determined both in mRNA reporter assays as well as in vivo. Our findings suggest a complex bifunctional role for Musashi1 in the control of pituitary cell function.
Assuntos
Hipófise , Proteínas de Ligação a RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Hipófise/metabolismo , Processamento de Proteína Pós-Traducional , Hormônios Hipofisários/metabolismoRESUMO
Introduction: Maternal obesity is associated with increased concentrations of human milk (HM) obesogenic hormones, pro-inflammatory cytokines, and oligosaccharides (HMOs) that have been associated with infant growth and adiposity. The objective of this pilot study was to determine if adherence to a Mediterranean meal plan during lactation modulates macronutrients and bioactive molecules in human milk from mothers with obesity. Methods: Sixteen healthy, exclusively breastfeeding women with obesity (body mass index ≥30 kg/m2) enrolled between 4 and 5 months postpartum. The women followed a 4-week Mediterranean meal plan which was provided at no cost. Maternal and infant anthropometrics, HM composition, and infant intakes were measured at enrollment and at weeks 2 and 4 of the intervention. Thirteen mother-infant dyads completed the study. Additionally, participants from an adjacent, observational cohort who had obesity and who collected milk at 5 and 6 months postpartum were compared to this cohort. Results: Participants' healthy eating index scores improved (+27 units, p < 0.001), fat mass index decreased (-4.7%, p < 0.001), and daily energy and fat intake were lower (-423.5 kcal/day, p < 0.001 and-32.7 g/day, p < 0.001, respectively) following the intervention. While HM macronutrient concentrations did not change, HM leptin, total human milk oligosaccharides (HMOs), HMO-bound fucose, Lacto-N-fucopentaose (LNFP)-II, LNFP-III, and difucosyllacto-N-tetrose (DFLNT) concentrations were lower following the intervention. Infant intakes of leptin, tumor necrosis factor (TNF)-α, total HMOs, HMO-bound fucose, LNFP-III and DFLNT were lower following the intervention. Specific components of the maternal diet (protein and fat) and specific measures of maternal diet quality (protein, dairy, greens and beans, fruit and vegetables) were associated with infant intakes and growth. Discussion: Adherence to a Mediterranean meal plan increases dietary quality while reducing total fat and caloric intake. In effect, body composition in women with obesity improved, HM composition and infants' intakes were modulated. These findings provide, for the first time, evidence-based data that enhancing maternal dietary quality during lactation may promote both maternal and child health. Longer intervention studies examining the impact of maternal diet quality on HM composition, infant growth, and infant development are warranted.
RESUMO
Background: Breastfeeding is widely recognized as the optimal feeding method for infants. However, breastfeeding goals are often unmet, especially in mothers with excessive weight. Potential factors associated with unmet goals could be disparities in care for women with higher body mass index (BMI) or mental health symptomology. Methods: Women enrolled in a longitudinal study were stratified by BMI into three groups: mothers with normal weight (18.5-24.9 kg/m2, n = 101), with overweight (25-29.9 kg/m2, n = 78), and with obesity (OB; 30-35 kg/m2, n = 48). Breastfeeding intention and standardized mental health questionnaires were administered at gestational weeks 12 and 36. The prevalence of initiation and duration of breastfeeding were determined based on self-reported breastfeeding start and end dates. Wilcoxon tests, pairwise proportion test, Cox proportional hazards regression, and linear regression were used. Results: Higher maternal weight status (OB) was significantly associated with lower breastfeeding intention and duration. As expected, higher breastfeeding intention scores were associated with significantly longer breastfeeding duration. Higher scores on the Beck Depression Inventory (BDI), associated with a greater number of depression symptoms, mediated the negative impact of weight status on breastfeeding intention. Conclusions: breastfeeding outcomes are negatively associated with maternal weight status and prenatal mental health with the relationship between the two being interconnected, despite subclinical scores on the BDI. Further research is needed to explore the role of mental health on breastfeeding outcomes. From these findings, targeted prenatal interventions for women with excessive weight and depressive symptoms would likely promote and improve breastfeeding outcomes. ClinicalTrials.gov: www.clinicaltrials.gov, ID #NCT01131117.