The Musashi RNA binding proteins direct the translational activation of key pituitary mRNAs.

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.

A Mediterranean diet plan in lactating women with obesity reduces maternal energy intake and modulates human milk composition - a feasibility study.

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.

The Impact of Excessive Weight on Breastfeeding Intention, Initiation, and Duration.

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.

Perspective: A Research Roadmap about Ultra-Processed Foods and Human Health for the United States Food System: Proceedings from an Interdisciplinary, Multi-Stakeholder Workshop.

Our objective was to convene interdisciplinary experts from government, academia, and industry to develop a Research Roadmap to identify research priorities about processed food intake and risk for obesity and cardiometabolic diseases (CMD) among United States populations. We convened attendees at various career stages with diverse viewpoints in the field. We held a "Food Processing Primer" to build foundational knowledge of how and why foods are processed, followed by presentations about how processed foods may affect energy intake, obesity, and CMD risk. Breakout groups discussed potential mechanistic and confounding explanations for associations between processed foods and obesity and CMD risk. Facilitators created research questions (RQs) based on key themes from discussions. Different breakout groups convened to discuss what is known and unknown for each RQ and to develop sub-RQs to address gaps. Workshop attendees focused on ultra-processed foods (UPFs; Nova Group 4) because the preponderance of evidence is based on this classification system. Yet, heterogeneity and subjectivity in UPF classification was a challenge for RQ development. The 6 RQs were: 1) What objective methods or measures could further categorize UPFs, considering food processing, formulation, and the interaction of the two? 2) How can exposure assessment of UPF intake be improved? 3) Does UPF intake influence risk for obesity or CMDs, independent of diet quality? 4) What, if any, attributes of UPFs influence ingestive behavior and contribute to excess energy intake? 5) What, if any, attributes of UPFs contribute to clinically meaningful metabolic responses? 6) What, if any, external environmental factors lead people to consume high amounts of UPFs? Uncertainty and complexity around UPF intake warrant further complementary and interdisciplinary causal, mechanistic, and methodological research related to obesity and CMD risk to understand the utility of applying classification by degree of processing to foods in the United States.

Education and Experiences of Antenatal Breast Milk Expression: A Systematic Review.

Background: Breastfeeding rates have stagnated recently despite recommendations to breastfeed until age 2 years. Antenatal breast milk expression (ABME) is a method used to prepare the breast for breastfeeding. However, there is limited evidence available on the benefits, risks, and impact of ABME on maternal-infant breastfeeding dyads. Methods: This review identified and summarized studies on women who engaged in ABME and their personal experiences. Databases searched included PubMed MEDLINE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and EMBASE. Initially, abstracts and titles were reviewed, and then, full-text studies were screened for inclusion by two blinded authors. Two authors assessed the quality of the studies using a standardized tool, two authors completed data extraction, and one author completed data harmonization into tables. Results: A total of 1,410 studies were identified (after duplicates removed) and 10 citations qualified for the inclusion criteria. Only two studies received an overall rating of strong quality and low-risk bias. The selected articles varied in primary outcomes; however, main focuses were experiences, knowledge, and perspective after practicing ABME. Data varied on timing of ABME, but most studies started between 34 and 36 weeks. The average amount of expressed milk was reported in four studies but was variable. Conclusions: This systematic review found that the literature is limited regarding ABME, and most studies were focused on women with diabetes. The current limited evidence suggests that ABME may be a helpful tool in improving maternal breastfeeding confidence and breastfeeding outcomes. Negative side effects reported related to ABME included difficulty learning the technique, discomfort, and feeling of awkwardness while expressing. Future research should focus on higher quality studies regarding use of ABME, proper teaching of ABME technique, and the use of ABME to improve breastfeeding outcomes in diverse populations of maternal-infant dyads.

Associations Between Maternal Physical Activity, Maternal Lipid Levels, and Infant Anthropometric Outcomes at Two Weeks of Age.

BACKGROUND: This study determined the relationship between physical activity (PA), circulating lipids throughout pregnancy and infant anthropometric outcomes at birth and 2 weeks of age. METHODS: Women (N = 234) with normal weight (NW, BMI 18.5-24.9 kg/m2) and with overweight and class I obesity (OW/OB, BMI 25-35 kg/m2) were categorized into high and low PA based on average cohort steps during pregnancy (8099 steps/day). Circulating fasting lipids were measured at each trimester. Standardized methods were used to obtain anthropometrics measures. Infant body composition was estimated by quantitative nuclear magnetic resonance (EchoMRI-AH small; ECHO Medical Systems). RESULTS: Women with NW who had higher activity had lower circulating triglycerides (TG) and total cholesterol (TC) levels at 12 weeks compared to women with NW and low activity (p < 0.05). Women with OW/OB and high activity level throughout pregnancy had lower circulating TG, and low density lipoprotein (LDL), at 12 weeks, lower LDL at 24 weeks, and lower TG at 36 weeks compared to the women with OW/OB who had low activity levels (p < 0.05). For children born to women with OW/OB, maternal circulating TG and LDL were most associated with infant anthropometrics at 2 weeks of age. CONCLUSION: This study supports that higher PA during pregnancy is associated with lower lipid levels throughout pregnancy with a greater effect size in women with OW/OB. Maternal lipids were associated with anthropometrics and infant body composition at two weeks of life in women with OW/OB.

Effect of a dietary and exercise intervention in women with overweight and obesity undergoing fertility treatments: protocol for a randomized controlled trial.

BACKGROUND: Distinct molecular, inflammatory, and metabolic signatures are present in oocytes and follicular fluid derived from women with obesity when compared to those derived from normal weight women, which suggest existing signals that may program future offspring for metabolic diseases. This study aims to assess the feasibility and efficacy of a peri-conception nutrition and exercise intervention on mitigating obesity-associated changes in oocyte gene expression profiles and follicular fluid metabolites. METHODS: This single blinded randomized control trial will include 120 women with a BMI of 25-45 kg/m2, ≥21 years of age, and undergoing in vitro fertilization (IVF) treatments. Participants will be randomized to standard of care (N = 60) or an intervention group (N = 60) in a block design by polycystic ovary syndrome status. The intervention will combine a dietary component (Mediterranean meal plan) with exercise prescription following the Physical Activity Guidelines for Americans. Participants will be assessed pre- and post-intervention. The standard of care group will be offered to join the intervention group if the IVF treatments are unsuccessful as a cross over design. Recruitment is anticipated to start in July of 2021. Primary outcomes will include single oocyte gene expression profiles and follicular fluid metabolites. Mann-Whitney U nonparametric tests will be used to assess potential differences for each stratum. Follicular fluid and serum metabolites will be analyzed using a one-factor Analysis of Covariance (ANCOVA) at four levels, pair-wise comparisons using Tukey-Kramer post-hoc tests will be used to identify groups whose means differ significantly while retaining the family-wise error rate at 5%. When the design is balanced, two-way Analysis of Variance (ANOVA), or non-parametric Friedman test will be used in data analysis. Additionally, general linear models and ANCOVA may be used to control for covariates. Significance will be set at p < 0.05. Findings will be disseminated via peer-reviewed manuscripts and presentations at scientific conferences. DISCUSSION: This study will provide novel data and key information on the impact of a dietary and exercise intervention on oocyte gene expression and follicular fluid content. Results will demonstrate the potential of such intervention in mitigating obesity-induced changes in oocyte gene expression and follicular fluid metabolites. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04273048 ): submitted November 13, 2019; posted February 17, 2020.