Prepregnancy plant-based diets and risk of hypertensive disorders of pregnancy.

BACKGROUND: Plant-based diets have been associated with a lower risk of cardiovascular disease in nonpregnant adults, but specific evidence for their effects on risk of hypertensive disorders of pregnancy is scarce. OBJECTIVE: This study aimed to evaluate the prospective association between adherence to plant-based diets before pregnancy and the risk for hypertensive disorders of pregnancy. We hypothesized that women with higher adherence to plant-based diets would have a lower risk for hypertensive disorders of pregnancy. STUDY DESIGN: We followed 11,459 parous women (16,780 singleton pregnancies) without chronic diseases, a history of preeclampsia, and cancers who participated in the Nurses' Health Study II (1991-2009), which was a prospective cohort study. Diet was assessed every 4 years using a validated food frequency questionnaire from which we calculated the plant-based diet index (higher score indicates higher adherence) to evaluate the health associations of plant-based diets among participants while accounting for the quality of plant-based foods. Participants self-reported hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension. We estimated the relative risk of hypertensive disorders of pregnancy in relation to plant-based diet index adherence in quintiles using generalized estimating equations log-binomial regression while adjusting for potential confounders and accounting for repeated pregnancies for the same woman. RESULTS: The mean (standard deviation) age at first in-study pregnancy was 35 (4) years. A total of 1033 cases of hypertensive disorders of pregnancy, including 482 cases of preeclampsia (2.9%) and 551 cases of gestational hypertension (3.3%) were reported. Women in the highest quintile of plant-based diet index were significantly associated with a lower risk for hypertensive disorders of pregnancy than women in the lowest quintile (relative risk, 0.76; 95% confidence interval, 0.62-0.93). There was an inverse dose-response relationship between plant-based diet index and risk for hypertensive disorders of pregnancy. The multivariable-adjusted relative risk (95% confidence interval) of hypertensive disorders of pregnancy for women in increasing quintiles of plant-based diet index were 1 (ref), 0.93 (0.78-1.12), 0.86 (0.72-1.03), 0.84 (0.69-1.03), and 0.76 (0.62-0.93) with a significant linear trend across quintiles (P trend=.005). This association was slightly stronger for gestational hypertension (relative risk, 0.77; 95% confidence interval, 0.60-0.99) than for preeclampsia (relative risk, 0.80; 95% confidence interval, 0.61-1.04). Mediation analysis suggested that body mass index evaluation for dietary assessment and pregnancy explained 39% (95% confidence interval, 15%-70%]) of the relation between plant-based diet index and hypertensive disorders of pregnancy and 48% (95% confidence interval, 12%-86%]) of the relation between plant-based diet index and gestational hypertension. CONCLUSION: Higher adherence to plant-based diets was associated with a lower risk of developing hypertensive disorders of pregnancy. Much of the benefit seems to be related to improved weight control.

Exploring the relationship between history of infertility and the experience of menopausal symptoms.

OBJECTIVE: The aim of the study is to examine longitudinal associations of history of infertility with menopausal symptoms in midlife. METHODS: Six hundred ninety-five midlife women (≥45 y old or reporting ≥12 mo of amenorrhea at the midlife visit) in Project Viva, a prospective cohort enrolled 1999-2002 during pregnancy and followed for 18 years after enrollment ("midlife visit"). Exposure was history of infertility defined as time to pregnancy ≥12 months (≥6 mo if ≥35 y), use of medical treatment to conceive, or infertility consultation or treatment in the 6-month preceding enrollment. The primary outcome was score below or above the median on the Menopause Rating Scale (MRS). Secondary outcomes included individual symptom score on the MRS and self-reported age of menopause. RESULTS: A total of 36.6% had a history of infertility in their lifetime. At the time of MRS completion, the women with prior infertility were older (53.4 [SD, 3.8] vs 51.2 [SD, 3.7] y) than those without infertility and a larger proportion had reached menopause (62% vs 40%). Women with prior infertility were more likely to score above the median on the MRS (Adjusted Odds Ratio [aOR], 1.45; 95% confidence interval [CI], 1.04-2.01) and had higher odds for reporting any depressive mood (aOR, 1.56; 95% CI, 1.12-2.16) and irritability (aOR, 1.57; 95% CI, 1.13-2.19). There was a trend toward greater severity of sleep problems among women with prior infertility. There was no association of prior infertility with report of other menopausal symptoms or age of menopause. CONCLUSIONS: Our findings suggest that women with prior infertility are more likely to have an MRS score above the median and experience depressive mood, irritability, and sleep problems during midlife than women without infertility. These findings have implications for mental health screening among midlife women.

Associations of age at first birth and lifetime parity with weight and adiposity across midlife in women from Project Viva.

OBJECTIVE: This study aimed to evaluate the associations of age at first birth and parity with weight, waist circumference (WC), and body fat across midlife. METHODS: A secondary data analysis was conducted with 735 participants from Project Viva who reported their age at first birth and lifetime parity at a midlife study visit. Weight, WC, and body fat were measured up to four times after the participants' final birth, and associations were examined using linear mixed-effects regression models. RESULTS: Participants' mean (SD) age was 32.6 (4.9) years at enrollment and 30.4 (5.5) years at their first birth, and they had 2.4 (0.9) lifetime births. In adjusted models, women who had their first birth at age <23 or ≥40 years, versus age 30 to 34 years, had a higher trajectory of weight, WC, and body fat after their final birth (i.e., mean differences in weight 8.38 kg [95% CI: 4.13-12.63] for age <23 years and 6.54 kg [95% CI: 0.64-12.45] for age ≥40 years). Women with four or more births, versus two, had a higher trajectory of adiposity after accounting for covariates. CONCLUSIONS: Women who have a first birth before age 23 years or after age 40 years and those with multiple births may benefit from more intensive monitoring for excess adiposity gain.

Self-reported menstrual cycle length during reproductive years in relation to menopausal symptoms at midlife in Project Viva.

OBJECTIVE: The aim of this study was to investigate the extent to which self-reported menstrual cycle length during reproductive years is associated with menopausal symptoms and age at natural menopause at midlife. METHODS: This analysis includes 634 women who enrolled in Project Viva during pregnancy (1999-2002) and completed the midlife visit approximately 18 years later. Women self-reported menstrual cycle length at enrollment (early pregnancy) and at midlife reported total and specific menopausal symptoms using the Menopause Rating Scale as well as age at natural menopause. We used linear and regression models to evaluate associations of cycle length with total and specific menopausal symptoms. We also applied a time-to-event Cox proportional hazards model to investigate the relationship between menstrual cycle length and onset of natural menopause. We adjusted models for age at midlife visit, prepregnancy body mass index, race/ethnicity, education, and parity. RESULTS: At enrollment (median age, 33.3 years), 90 (14%) women reported having short (≤25 days) and 39 (6%) reported long (≥35 days) menstrual cycles. Compared with women with a normal menstrual cycle length of 26 to 34 days, women whose cycles were short had a higher total Menopause Rating Scale at midlife ( ß = 2.05; 95% confidence interval [CI], 0.73-3.38). Specifically, women with short menstrual cycles during their reproductive years had higher odds of midlife sleep problems (odds ratio [OR], 1.92; 95% CI, 1.10-3.37), heart discomfort (OR, 1.68; 95% CI, 1.03-2.73), and depressive symptoms (OR, 1.85; 95% CI, 1.16-2.96). In addition, compared with women with a normal cycle length of 26 to 34 days, women reporting short cycles had an earlier onset of natural menopause (hazard ratio, 1.67; 95% CI, 1.11-2.51). CONCLUSIONS: Compared with women with normal menstrual cycle length, those with short menstrual cycles during their reproductive years had a higher frequency of total and certain menopausal symptoms at midlife and reached menopause earlier.

Associations of hypertensive disorders of pregnancy and gestational diabetes mellitus with menopausal symptoms at midlife in Project Viva.

OBJECTIVE: The aim of this study was to evaluate the associations of a lifetime history of hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) with menopausal symptoms in midlife. METHODS: This was a secondary analysis of women participating in Project Viva, an ongoing cohort enrolled during pregnancy. The exposure was lifetime history of HDP or GDM assessed for the index pregnancy by review of outpatient and hospital medical records and for all other pregnancies by interview or questionnaire at study entry (1999-2002) and the midlife visit (2017-2021). The primary outcome was the Menopause Rating Scale (MRS) applied at the midlife study visit. We used linear or logistic regression models adjusted for covariates such as baseline age, race/ethnicity, education, married/cohabiting, household income, baseline parity, age at menarche, and body mass index at midlife. RESULTS: Of the 676 included participants, 120 (18%) had a history of HDP, and 47 (7%) had a history of GDM. The mean (SD) age was 52 (3.9) years at the midlife visit, and 48% of the participants had experienced menopause. There were no consistent differences in total, domain-specific, or individual symptoms in women with a history of HDP or GDM. A history of HDP and/or GDM was not associated with age at the onset of natural menopause. CONCLUSIONS: Our findings do not support an association of a history of HDP or GDM with the severity of menopausal symptoms or age at the onset of natural menopause. Larger studies of women with a history of these pregnancy complications are needed to clarify their association with menopausal symptoms.

Development of microsatellites markers for the deep coral Madracis myriaster (Pocilloporidae: Anthozoa).

In 2013 Colombia made an important step towards the construction and management of Marine Protected Areas (MPAs) by establishing the first Deep Corals National Park (PNNCP). Inside this MPA, the coral Madracis myriaster (Cnidaria: Pocilloporidae) was found as the main reef builder, offering habitat for many species of fish and invertebrates. In order to improve the study of deep-sea coral habitats, their connectivity and prospective management, nine new genetic markers (microsatellites) were developed for M. myriaster and tested in samples from PNNCP. We present the assessment of these markers, with a specificity for the deep coral, and its prospective use in future analysis for the PNNCP and other areas in the Caribbean and the Atlantic, where M. myriaster is reported. We also include an additional taxonomic analysis performed on samples of M. myriaster using scanning electron microscopy.

Increasing Representation of Epidemiologists From Around the World in the Society for Epidemiologic Research: The Case of Mexico.

Mexico has a population of 129 million and is considered one of the most unequal countries in the world, suffering from widespread health disparities. There is a pressing need to strengthen epidemiologic capacity in Mexico, to help solve the complex health problems the country faces and to reduce health inequities. However, the representation of Mexican epidemiologists in the largest epidemiologic society in North America is low, despite the short distance to the United States. In this commentary, we discuss the barriers to higher representation of Mexican epidemiologists within the Society for Epidemiologic Research (SER), including language barriers, costs, and regional necessities. We also discuss opportunities to expand Mexican SER representation and collaboration. Overall, we hope that this is a call towards expanding SER global participation and starting a conversation on a common agenda for epidemiologic research.

History of infertility and pregnancy outcomes in Project Viva: a prospective study.

BACKGROUND: Infertility has been associated with the risk of adverse pregnancy outcomes. It is not clear whether infertility and underlying causes of infertility or the use of medically assisted reproduction (MAR) therapies are responsible for the observed associations. In this study, we aimed to evaluate the association of history of infertility with pregnancy outcomes and identify whether the associations, if present, differed by subgroups defined by the use of MAR. METHODS: Prospective study of 2201 pregnant women from the Boston-area Project Viva cohort. The exposure was history of infertility based on self-reported time to pregnancy ≥12 mo (or ≥ 6 mo if ≥35 y) or use of MAR; a diagnosis of infertility or claims for infertility treatments from medical records. The outcomes included: gestational glucose tolerance (gestational diabetes, impaired glucose tolerance, isolated hyperglycemia vs. normoglycemia), hypertensive disorders (gestational hypertension/preeclampsia vs. normotension), gestational weight gain (inadequate/excessive vs. adequate), systolic (SBP) and diastolic blood pressure, birthweight-for-gestational age z-score (tertile 2 and 3 vs. 1), preterm birth (<37 vs. ≥37 weeks at delivery), and birth outcome (pregnancy loss vs. live birth). We performed linear and logistic/multinomial regression analyses adjusted for age, race/ethnicity, age at menarche, pre-pregnancy BMI, and prenatal smoking. RESULTS: Mean (SD) age was 32.0 (5.0) years, and 18.8% of women had history of infertility, 32.6% of whom used MAR. SBP across pregnancy was 0.72 mmHg higher in women with vs. without infertility (95% CI 0.02, 1.42). The associations were stronger among women who used MAR (ß 1.32 mmHg, 95% CI 0.21, 2.44), especially among those who used gonadotropins or gonadotropin-releasing hormone [GnRH] agonists (ß 1.91 mmHg, 95% CI 0.48, 3.35). Other outcomes were not associated with history of infertility. CONCLUSIONS: A history of infertility was associated with higher SBP during pregnancy, with stronger associations among those who used gonadotropins or GnRH agonists. Future studies are needed to confirm these findings and determine their clinical implications.

History of infertility and long-term weight, body composition, and blood pressure among women in Project Viva.

PURPOSE: To evaluate the association of a history of infertility with long-term weight, body composition, and blood pressure. METHODS: We studied 1581 women from the prospective cohort Project Viva. History of infertility was based on self-reported time to pregnancy ≥12 months or use of medical treatment to conceive for the index or any prior pregnancy; a diagnosis of infertility; claims for infertility treatments/prescriptions abstracted from medical records. The outcomes were weight, waist circumference, and body fat assessed through 12 years postpartum; and blood pressure assessed through 3 years postpartum. We used linear mixed-effect models adjusted for age, race/ethnicity, income, education, marital status, parity, and age at menarche. RESULTS: Three hundred forty-two women (21.6%) had a history of infertility. In adjusted models, women with versus without infertility, had higher average weight (3.29 kg, 95% confidence interval [CI]: 1.35-5.24), waist circumference (2.46 cm, 95% CI: 0.78-4.13) and body fat (1.76 kg, 95% CI: 0.09-3.43). Among younger (18-29 years), but not older (≥30 years) women, infertility was associated with higher systolic (4.08 mmHg, 95% CI: 0.93, 7.23) and diastolic blood pressure (2.16 mmHg, 95% CI: 0.11-4.20). CONCLUSIONS: A history of infertility may serve as a marker to identify women at higher cardiometabolic risk.

Intermediate- and long-term associations between air pollution and ambient temperature and glycated hemoglobin levels in women of child bearing age.

BACKGROUND: Air pollution has been linked to obesity while higher ambient temperatures typically reduce metabolic demand in a compensatory manner. Both relationships may impact glucose metabolism, thus we examined the association between intermediate- and long-term exposure to fine particulate matter (PM2.5) and ambient temperature and glycated hemoglobin(HbA1c), a longer-term marker of glucose control. METHODS: We assessed 3-month, 6-month, and 12-month average air pollution and ambient temperature at 1-km2 spatial resolution via satellite remote sensing models (2013-2019), and assessed HbA1c at four, six, and eight years postpartum in women enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City. PM2.5 and ambient temperature were matched to participants' addresses and confirmed by GPS tracker. Using linear mixed-effects models, we examined the association between 3-month, 6-month, and 12-month average PM2.5 and ambient temperature with repeated log-transformed HbA1c values. All models included a random intercept for each woman and were adjusted for calendar year, season, and individual-level confounders (age, marital status, smoking, alcohol consumption level, and education level). RESULTS: We analyzed 1,265 HbA1c measurements of 484 women. Per 1 µg/m3 increase in 3-month and 6-month PM2.5, HbA1c levels increased by 0.28% (95% confidence interval (95 %CI): 0.14, 0.42%) and 0.28% (95 %CI: 0.04, 0.52%) respectively. No association was seen for 12-month average PM2.5. Per 1 °C increase in ambient temperature, HbA1c levels decreased by 0.63% (95 %CI: -1.06, -0.21%) and 0.61% (95 %CI: -1.08, -0.13%), while the 12-month average again is not associated with HbA1c. CONCLUSIONS: Intermediate-term exposure to PM2.5 and ambient temperature are associated with opposing changes in HbA1c levels, in this region of high PM2.5 and moderate temperature fluctuation. These effects, measurable in mid-adult life, may portend future risk of type 2 diabetes and possible heart disease.

Prenatal phthalates, gestational weight gain, and long-term weight changes among Mexican women.

BACKGROUND: Phthalates are endocrine disrupting chemicals that may influence weight status; however, few studies have considered weight gain during pregnancy and subsequent long-term weight changes in women. OBJECTIVE: To determine associations of prenatal phthalate exposure with maternal weight during pregnancy and through up to seven years post-delivery. METHODS: We analyzed 15 urinary phthalate biomarker concentrations during the 2nd and 3rd trimesters among 874 pregnant women enrolled in the Programming Research in Obesity, Growth Environment and Social Stress Study in Mexico City. We examined three time-specific maternal weight outcomes: gestational weight gain (between 2nd and 3rd trimesters), short-term weight (between 3rd trimester and 12 months post-delivery), and long-term weight (between 18 months and 6-7 years post-delivery). We used Bayesian Kernel Machine Regression (BKMR) to estimate associations for the total phthalate mixture, as well as multivariable linear mixed models for individual phthalate biomarkers. RESULTS: As a mixture, 2nd trimester urinary phthalate biomarker concentrations were associated with somewhat lower gestational weight gain between the 2nd and 3rd trimesters (interquartile range, IQR, difference: -0.07 standard deviations, SD; 95% credible interval, CrI: -0.20, 0.06); multivariable regression and BKMR models indicated that this inverse association was primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP). Prenatal (2nd and 3rd trimesters) urinary phthalate mixture concentrations were positively associated with maternal weight change through 12 months postpartum (IQR difference: 0.11 SD; 95% CrI: 0.00, 0.23); these associations persisted from 18 months to 6-7 years follow-up (IQR difference: 0.07 SD; 95% CrI: 0.04, 0.10). Postpartum weight changes were associated with mono-3-carboxypropyl phthalate (MCPP) and MECPTP. CONCLUSIONS: Prenatal phthalate exposure was inversely associated with gestational weight gain and positively associated with long-term changes in maternal weight. Further investigation is required to understand how phthalates may influence body composition and whether they contribute to the development of obesity and other cardiometabolic diseases in women.

Menstrual cycle length and adverse pregnancy outcomes among women in Project Viva.

BACKGROUND: Retrospective studies suggest that menstrual cycle length may be a risk marker of adverse pregnancy outcomes, but this evidence is susceptible to recall bias. OBJECTIVE: To evaluate the prospective association between menstrual cycle length and the risk of adverse pregnancy outcomes. METHODS: Secondary analysis of 2046 women enrolled in Project Viva at ~10 weeks of gestation and followed through delivery. The exposure was menstrual cycle length. The outcomes included gestational glucose tolerance (gestational diabetes/impaired glucose tolerance [GDM/IGT] and isolated hyperglycaemia), hypertensive disorders of pregnancy (gestational hypertension/preeclampsia), gestational weight gain, birthweight-for-gestational age z-scores (BWZ) categorised in tertiles, preterm birth and birth outcome (live birth and pregnancy loss). We used modified Poisson and multinomial logistic regression adjusted for age, race/ethnicity, parity, age at menarche and pre-pregnancy body mass index. RESULTS: Mean (SD) age at enrolment was 32.1 (4.9) years. Most women (74.3%) had a cycle length of 26-34 days (reference group), 16.2% reported short cycles (≤25 days), and 9.5% reported long/irregular cycles (≥35 days/too irregular to estimate). Compared with the reference group, women with short cycles had lower odds of GDM/IGT (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.28, 0.89), whereas women with long/irregular cycles had higher odds (OR 1.72, 95% CI 1.04, 2.83). Additionally, women with short cycles had higher odds of having a newborn in the lowest tertile of BWZ (OR 1.45, 95% CI 1.06, 1.98). There was a U-shaped relation between cycle length and preterm birth with both short (relative risk [RR] 1.49, 95% CI 0.98, 2.27) and long/irregular (RR 2.04, 95% CI 1.30, 3.20) cycles, associated with a higher risk. CONCLUSIONS: Variation in menstrual cycle length may be a risk marker of GDM/IGT, lower birth size and preterm birth and flag women who may benefit from targeted monitoring and care before and during pregnancy.

Exposición a químicos disruptores endócrinos obesogénicos y obesidad en niños y jóvenes de origen latino o hispano en Estados Unidos y Latinoamérica: una perspectiva del curso de la vida.

En el 2019, en seguimiento a un taller dirigido por el Global Health Studies del Fogarty International Center sobre el tema de la prevención de la obesidad infantil y las sinergias de investigación que surgen a través de las colaboraciones transfronterizas, convocamos a un grupo de expertos de Estados Unidos y Latinoamérica para que realizaran una revisión narrativa de la literatura epidemiológica sobre el papel obesogénico de los químicos disruptores endócrinos (EDC, por sus siglas en inglés) en la etiología de la obesidad infantil entre la juventud latina de Estados Unidos y Latinoamérica. Además de resumir y sintetizar los resultados de las investigaciones sobre este tema publicados en la última década, contextualizamos los hallazgos dentro de un marco bioconductual de curso de vida para identificar relaciones exposición-desenlace impulsadas por resultados de investigación, identificar inconsistencias y deficiencias de la literatura actual, y discutir el papel de las regulaciones políticas, todo con el objetivo de identificar posibles vías para la prevención temprana de la obesidad en las poblaciones hispanas/latinas.

Exposure to obesogenic endocrine disrupting chemicals and obesity among youth of Latino or Hispanic origin in the United States and Latin America: A lifecourse perspective.

Following a 2019 workshop led by the Center for Global Health Studies at the Fogarty International Center on the topic of childhood obesity prevention and research synergies transpiring from cross-border collaborations, we convened a group of experts in the United States and Latin America to conduct a narrative review of the epidemiological literature on the role of obesogenic endocrine disrupting chemicals (EDCs) in the etiology of childhood obesity among Latino youth in the United States and Latin America. In addition to summarizing and synthesizing results from research on this topic published within the last decade, we place the findings within a lifecourse biobehavioral framework to aid in identification of unique exposure-outcome relationships driven by both biological and behavioral research, identify inconsistencies and deficiencies in current literature, and discuss the role of policy regulations, all with the goal of identifying viable avenues for prevention of early life obesity in Latino/Hispanic populations.

Single-cell analysis by mass cytometry reveals metabolic states of early-activated CD8+ T cells during the primary immune response.

Memory T cells are thought to rely on oxidative phosphorylation and short-lived effector T cells on glycolysis. Here, we investigated how T cells arrive at these states during an immune response. To understand the metabolic state of rare, early-activated T cells, we adapted mass cytometry to quantify metabolic regulators at single-cell resolution in parallel with cell signaling, proliferation, and effector function. We interrogated CD8+ T cell activation in vitro and in response to Listeria monocytogenes infection in vivo. This approach revealed a distinct metabolic state in early-activated T cells characterized by maximal expression of glycolytic and oxidative metabolic proteins. Cells in this transient state were most abundant 5 days post-infection before rapidly decreasing metabolic protein expression. Analogous findings were observed in chimeric antigen receptor (CAR) T cells interrogated longitudinally in advanced lymphoma patients. Our study demonstrates the utility of single-cell metabolic analysis by mass cytometry to identify metabolic adaptations of immune cell populations in vivo and provides a resource for investigations of metabolic regulation of immune responses across a variety of applications.

Weight Trajectories After Delivery are Associated with Adiposity and Cardiometabolic Markers at 3 Years Postpartum Among Women in Project Viva.

BACKGROUND: Postpartum weight trajectories and its implications on later cardiometabolic health are not entirely understood. OBJECTIVES: Our objectives were: 1) to characterize maternal weight trajectories from 1 to 24 mo postpartum, 2) to determine the association of prepregnancy BMI, gestational weight gain (GWG), and pregnancy behaviors with the trajectories, and 3) to evaluate the association of weight trajectories with BMI, waist circumference (WC), lipid profile, glucose, insulin resistance, blood pressure, and inflammatory markers at 3 y postpartum. METHODS: We studied 1359 mothers from the prospective cohort Project Viva. Using weights at 1, 6, 12, and 24 mo postpartum, we characterized weight trajectories using a latent class growth model. For objectives 2 and 3, we used multinomial logistic regression and multiple linear regression models, respectively. RESULTS: Around 85% of women fell into a trajectory of sustained weight loss (1-12 mo) + maintenance (12-24 mo) (reference), 5.7% followed a trajectory characterized by fast weight loss + slight gain, and 9.7% fell into a trajectory of little weight loss + slight gain. Prepregnancy overweight and obesity increased the odds of falling into the fast weight loss + slight gain trajectory, compared with the reference. Prepregnancy overweight [OR 1.57 (95% CI: 1.01, 2.46)] and a higher total GWG rate [3.69 (2.90, 4.68)] increased the odds of falling into the little weight loss + slight gain trajectory, whereas a higher Prudent dietary pattern score was protective [0.73 (0.54, 0.98)]. Women in this trajectory had higher BMI, WC, weight gain from prepregnancy, low-density lipoprotein cholesterol, and inflammatory markers at 3 y postpartum. CONCLUSIONS: Women following a trajectory of little weight loss + slight gain during the first 2 y postpartum had an adverse cardiometabolic profile 3 y after delivery. Targeting diet and GWG during pregnancy and facilitating postpartum weight loss could improve women's long-term health.

Patterns of Weight Change One Year after Delivery Are Associated with Cardiometabolic Risk Factors at Six Years Postpartum in Mexican Women.

Pregnancy is a contributor to the obesity epidemic in women, probably through postpartum weight retention (PPWR), weight gain (PPWG), or a combination of both (PPWR + WG). The contribution of these patterns of postpartum weight change to long-term maternal health remains understudied. In a secondary analysis of 361 women from the prospective cohort PROGRESS, we evaluated the associations between patterns of weight change one year after delivery and cardiometabolic risk factors at six years postpartum. Using principal component analysis, we grouped cardiometabolic risk factors into: (1) body mass index (BMI), waist circumference (WC), homeostatic model assessment of insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), and glucose; (2) systolic (SBP) and diastolic blood pressure (DBP); and (3) low-density lipoprotein cholesterol and total cholesterol. Using path analysis, we studied direct (patterns of weight change-outcomes) and indirect associations through BMI at six years postpartum. Around 60% of women returned to their pregestational weight (reference) by one year postpartum, 6.6% experienced PPWR, 13.9% PPWG, and 19.9% PPWR + WG. Women with PPWR + WG, vs. the reference, had higher BMI and WC at six years (2.30 kg/m2, 95% CI [1.67, 2.93]; 3.38 cm [1.14, 5.62]). This was also observed in women with PPWR (1.80 kg/m2 [0.80, 2.79]; 3.15 cm [-0.35, 6.65]) and PPWG (1.22 kg/m2 [0.53, 1.92]; 3.32 cm [0.85, 5.78]). PPWR + WG had a direct association with HOMA-IR (0.21 units [0.04, 0.39]). The three patterns of weight change, vs. the reference, had significant indirect associations with HOMA-IR, glucose, TG, HDL-c, SBP, and DBP through BMI at six years. In conclusion, women with PPWR + WG are at high-risk for obesity and insulin resistance. Interventions targeting women during pregnancy and the first year postpartum may have implications for their long-term risk of obesity and cardiovascular disease.

ERα Signaling Increased IL-17A Production in Th17 Cells by Upregulating IL-23R Expression, Mitochondrial Respiration, and Proliferation.

Women have increased prevalence of Th17-mediated autoimmune diseases, including lupus and multiple sclerosis, and severe asthma. While estradiol and progesterone increased IL-17A production in Th17 cells by inhibiting Let7f miRNA expression and increasing IL-23 receptor (IL-23R) expression, it remained unclear how estrogen signaling through the canonical nuclear receptors, estrogen receptor α (ERα) and/or ERß, regulated this pathway. We hypothesized that estrogen signaling through ERα increased IL-23R expression and IL-17A production from Th17 cells. To test this hypothesis, naïve T cells from WT female, WT male, Esr1-/- and Esr2-/- female mice were differentiated into Th17 cells. IL-17A production and IL-23R expression were significantly increased in Th17 cells from WT female mice compared to Th17 cells from WT male mice. Deletion of ERα (Esr1-/-), but not ERß (Esr2-/-), significantly decreased IL-17A production and IL-23R expression in Th17 cells by limiting IL-23R expression in a Let-7f dependent manner. ERα deficiency also decreased Th17 cell proliferation as well as decreased T cell metabolism as measured by ATP-linked oxygen consumption rate and proton leakage. Further, we found that Cox20 expression, a protein involved in mitochondrial respiration through assembly of cytochrome c oxidase in the electron transport chain, was increased in Th17 cells from WT female mice compared to Th17 cells from WT male and Esr1-/- female mice. Inhibition of Cox20 decreased IL-17 production in Th17 cells from WT female mice. Combined these studies showed that ERα signaling increased IL-17A production in Th17 cells by upregulating IL-23R expression and promoting mitochondrial respiration and proliferation.

Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism.

Activated T cells differentiate into functional subsets with distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to support the tricarboxylic acid cycle and redox and epigenetic reactions. Here, we identify a key role for GLS in T cell activation and specification. Though GLS deficiency diminished initial T cell activation and proliferation and impaired differentiation of Th17 cells, loss of GLS also increased Tbet to promote differentiation and effector function of CD4 Th1 and CD8 CTL cells. This was associated with altered chromatin accessibility and gene expression, including decreased PIK3IP1 in Th1 cells that sensitized to IL-2-mediated mTORC1 signaling. In vivo, GLS null T cells failed to drive Th17-inflammatory diseases, and Th1 cells had initially elevated function but exhausted over time. Transient GLS inhibition, however, led to increased Th1 and CTL T cell numbers. Glutamine metabolism thus has distinct roles to promote Th17 but constrain Th1 and CTL effector cell differentiation.

Differential glucose requirement in skin homeostasis and injury identifies a therapeutic target for psoriasis.

Proliferating cells, compared with quiescent cells, are more dependent on glucose for their growth. Although glucose transport in keratinocytes is mediated largely by the Glut1 facilitative transporter, we found that keratinocyte-specific ablation of Glut1 did not compromise mouse skin development and homeostasis. Ex vivo metabolic profiling revealed altered sphingolipid, hexose, amino acid, and nucleotide metabolism in Glut1-deficient keratinocytes, thus suggesting metabolic adaptation. However, cultured Glut1-deficient keratinocytes displayed metabolic and oxidative stress and impaired proliferation. Similarly, Glut1 deficiency impaired in vivo keratinocyte proliferation and migration within wounded or UV-damaged mouse skin. Notably, both genetic and pharmacological Glut1 inactivation decreased hyperplasia in mouse models of psoriasis-like disease. Topical application of a Glut1 inhibitor also decreased inflammation in these models. Glut1 inhibition decreased the expression of pathology-associated genes in human psoriatic skin organoids. Thus, Glut1 is selectively required for injury- and inflammation-associated keratinocyte proliferation, and its inhibition offers a novel treatment strategy for psoriasis.