ABSTRACT
Besides the well-recognized influence of maternal health on fetal in utero development, recent epidemiological studies appoint paternal pre-conception metabolic health as a significant factor in shaping fetal metabolic programming and subsequently offspring metabolic health; however, mechanisms behind these adaptations remain confined to animal models. To elucidate the effects of paternal obesity (P-OB) on infant metabolism in humans, we examined mesenchymal stem cells (MSCs) which give rise to infant tissue, remain involved in mature tissue maintenance, and resemble the phenotype of the offspring donor. Here, we assessed mitochondrial functional capacity, content, and insulin action in MSC from infants of fathers with overweight (BMI 25-30kg/m2) (P-OW) or obesity (BMI≥30kg/m2) (P-OB), while controlling for maternal intrauterine environment. Compared to P-OW, infant MSCs in the P-OB group had lower intact cell respiration, OXPHOS, and electron transport system capacity, independent of any changes in mitochondrial content. Furthermore, glucose handling, insulin action, and lipid content and oxidation were similar between groups. Importantly, infants in the P-OB group had a greater weight-to-length ratio, which could be in part due to changes in MSC metabolic functioning which precedes and therefore influences infant growth trajectories. These data suggest that P-OB negatively influences infant MSC mitochondria.
ABSTRACT
Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. While there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multi-center study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a pre-clinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 weeks of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 weeks. The adult component also includes recruitment of highly active endurance trained or resistance trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.
ABSTRACT
BACKGROUND AND AIM: Elevated fasting plasma lactate concentrations are evident in individuals with metabolic diseases. However, it has yet to be determined if these associations exist in a young, healthy population as a possible early marker for metabolic disease risk. The purpose of this study was to determine if indices of the metabolic syndrome are related to plasma lactate concentrations in this population. METHODS: Fifty (29 ± 7 yr) men (n = 19) and women (n = 31) classified as overweight (26.4 ± 1.8 kg/m2) participated in this observational study. Blood pressure and blood metabolites were measured after an overnight fast. Lactate was also measured before and after a three-day eucaloric high-fat (70 %) diet. The homeostatic model assessment for insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Visceral adipose tissue mass was determined via dual X-ray absorptiometry. RESULTS: Triglycerides (r = 0.55, p=<0.0001), HOMA-IR (r = 0.53, p=<0.0001), and systolic and diastolic (both, r = 0.36, p = 0.01) blood pressures associated with fasting plasma lactate. No differences in visceral adipose tissue existed between the sexes (p = 0.41); however, the relationship between visceral adipose tissue and lactate existed only in females (r = 0.59, p = 0.02) but not in males (p = 0.53). Fasting lactate and HOMA-IR increased in males (p = 0.01 and p = 0.02, respectively), but not females, following a three-day high-fat diet. CONCLUSION: Indices of the metabolic syndrome associated with fasting plasma lactates in young relatively healthy individuals. Fasting lactate also increased in a sex-specific manner after a three-day high fat diet. Thus, lactate could become a clinical marker for metabolic disease risk.
Subject(s)
Insulin Resistance , Metabolic Syndrome , Female , Humans , Male , Biomarkers , Fasting , Insulin , Lactic Acid , Obesity/complications , Young Adult , AdultABSTRACT
OBJECTIVE: In adults, skeletal muscle insulin sensitivity (SI ) and fatty acid oxidation (FAO) are linked with a predisposition to obesity. The current study aimed to determine the effects of maternal exercise on a model of infant skeletal muscle tissue (differentiated umbilical cord mesenchymal stem cells [MSCs]) SI and FAO and analyzed for associations with infant body composition. METHODS: Females <16 weeks' gestation were randomized to either 150 min/wk of moderate-intensity aerobic, resistance, or combination exercise or a nonexercising control. At delivery, MSCs were isolated from umbilical cords and myogenically differentiated, and SI and FAO were measured using radiolabeled substrates. Infant body fat percentage (BF%) and fat-free mass were calculated using standard equations at 1 and 6 months of age. RESULTS: MSCs from infants of all exercisers had significantly (p < 0.05) higher SI . MSC SI was inversely associated with infant BF% at 1 (r = -0.38, p < 0.05) and 6 (r = -0.65, p < 0.01) months of age. Infants with high SI had lower BF% at 1 (p = 0.06) and 6 (p < 0.01) months of age. MSCs in the high SI group had higher (p < 0.05) FAO. CONCLUSIONS: Exposure to any type of exercise in utero improves offspring SI and could reduce adiposity in early infancy.
Subject(s)
Insulin Resistance , Mesenchymal Stem Cells , Female , Humans , Infant , Adiposity , Body Composition , Mesenchymal Stem Cells/metabolism , Obesity/metabolismABSTRACT
Individuals with insulin resistance and obesity display higher skeletal muscle production of nonoxidized glycolytic products (i.e., lactate), and lower complete mitochondrial substrate oxidation to CO2. These findings have also been observed in individuals without obesity and are associated with an increased risk for metabolic disease. The purpose of this study was to determine if substrate preference is evident at the earliest stage of life (birth) and to provide a clinical blood marker (lactate) that could be indicative of a predisposition for metabolic disease later. We used radiolabeled tracers to assess substrate oxidation and insulin sensitivity of myogenically differentiated mesenchymal stem cells (MSCs), a proxy of infant skeletal muscle tissue, derived from umbilical cords of full-term infants. We found that greater production of nonoxidized glycolytic products (lactate, pyruvate, alanine) is directly proportional to lower substrate oxidation and insulin sensitivity in MSCs. In addition, we found an inverse relationship between the ratio of complete glucose oxidation to CO2 and infant blood lactate at 1 mo of age. Collectively, considering that higher lactate was associated with lower MSC glucose oxidation and has been shown to be implicated with metabolic disease, it may be an early indicator of infant skeletal muscle phenotype.NEW & NOTEWORTHY In infant myogenically differentiated mesenchymal stem cells, greater production of nonoxidized glycolytic products was directly proportional to lower substrate oxidation and insulin resistance. Glucose oxidation was inversely correlated with infant blood lactate. This suggests that innate differences in infant substrate oxidation exist at birth and could be associated with the development of metabolic disease later in life. Clinical assessment of infant blood lactate could be used as an early indicator of skeletal muscle phenotype.
Subject(s)
Insulin Resistance , Mesenchymal Stem Cells , Humans , Carbon Dioxide , Glycolysis/physiology , Glucose/metabolism , Muscle, Skeletal/metabolism , Obesity/metabolism , Lactic Acid/metabolism , Pyruvic Acid/metabolism , Mesenchymal Stem Cells/metabolism , Insulin/metabolismABSTRACT
Type 2 diabetes is more prevalent in African American (AA) than Caucasian (C) adults. Furthermore, differential substrate utilization has been observed between AA and C adults, but data regarding metabolic differences between races at birth remains scarce. The purpose of the present study was to determine if there are racial differences in substrate metabolism evident at birth using a mesenchymal stem cells (MSCs) collected from offspring umbilical cords. Using radio-labeled tracers, MSCs from offspring of AA and C mothers were tested for glucose and fatty acid metabolism in the undifferentiated state and while undergoing myogenesis in vitro. Undifferentiated MSCs from AA exhibited greater partitioning of glucose toward nonoxidized glucose metabolites. In the myogenic state, AA displayed higher glucose oxidation, but similar fatty acid oxidation rates. In the presence of both glucose and palmitate, but not palmitate only, AA exhibit a higher rate of incomplete fatty acid oxidation evident by a greater production of acid-soluble metabolites. Myogenic differentiation of MSCs elicits an increase in glucose oxidation in AA, but not in C. Together, these data suggest that metabolic differences between AA and C races exist at birth.NEW & NOTEWORTHY African Americans, when compared with Caucasians, display greater insulin resistance in skeletal muscle. Differences in substrate utilization have been proposed as a factor for this health disparity; however, it remains unknown how early these differences manifest. Using infant umbilical cord-derived mesenchymal stem cells, we tested for in vitro glucose and fatty acid oxidation differences. Myogenically differentiated MSCs from African American offspring display higher rates of glucose oxidation and incomplete fatty acid oxidation.
Subject(s)
Diabetes Mellitus, Type 2 , Mesenchymal Stem Cells , Adult , Humans , Infant , Infant, Newborn , Black or African American , Diabetes Mellitus, Type 2/metabolism , Fatty Acids/metabolism , Glucose/metabolism , Insulin/metabolism , Mesenchymal Stem Cells/metabolism , White PeopleABSTRACT
PURPOSE: Few studies examine whether maternal and neonatal outcomes differ by time from metabolic and bariatric surgery (MBS) to conception. We describe maternal and neonatal outcomes among women with pregnancy after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) overall and by whether conception occurred during the period when pregnancy is not recommended (< 18 months postoperative) versus later. MATERIALS AND METHODS: A prospective cohort study enrolled 135 US adult women (median age, 30 years, body mass index [BMI], 47.2 kg/m2) who underwent RYGB or SG (2006-2009) and subsequently reported ≥ 1 pregnancy within 7 years. Participants self-reported pregnancy-related information annually. Differences in prevalence of maternal and neonatal outcomes by postoperative conception timeframe (< 18 versus ≥ 18 months) were assessed. RESULTS: Thirty-one women reported ≥ 2 postoperative pregnancies. At time of postoperative conception (median 26 [IQR:22-52] months postoperative) median BMI was 31 (IQR:27-36) kg/m2. Excessive gestational weight gain (55%), cesarean section (42%) and preterm labor or rupture of membranes (40%) were the most common maternal outcomes. Forty percent of neonates had a composite outcome of still birth (1%), preterm birth (26%), small for gestational age (11%), or neonatal intensive care unit admission (8%). Prevalence of outcomes did not statistically significantly differ by timeframe. CONCLUSION: In US women who conceived ≤ 7 years following RYGB or SG, 40% of neonates had the composite neonatal outcome. The prevalence of maternal and neonatal outcomes post-MBS were not statistically significant by conception timeframe.
Subject(s)
Gastric Bypass , Obesity, Morbid , Premature Birth , Adult , Humans , Infant, Newborn , Female , Pregnancy , Obesity, Morbid/surgery , Prospective Studies , Cesarean Section , Retrospective Studies , Premature Birth/epidemiology , Premature Birth/surgery , Weight Gain , GastrectomyABSTRACT
CONTEXT: Maternal exercise positively influences pregnancy outcomes and metabolic health in progeny; however, data regarding the effects of different modes of prenatal exercise on offspring metabolic phenotype is lacking. OBJECTIVE: To elucidate the effects of different modes of maternal exercise on offspring umbilical cord derived mesenchymal stem cell (MSC) metabolism. DESIGN: Randomized controlled trial. SETTING: Clinical research facility. PATIENTS: Healthy females between 18 and 35 years of age and <16 weeks' gestation. INTERVENTION: Women were randomized to either 150 minutes of moderate intensity aerobic, resistance (RE), or combination exercise per week or to a non-exercising control. MAIN OUTCOME MEASURES: At delivery, MSCs were isolated from the umbilical cords. MSC glucose and fatty acid(s) metabolism was assessed using radiolabeled substrates. RESULTS: MSCs from offspring of all the exercising women demonstrated greater partitioning of oleate (P ≤ 0.05) and palmitate (P ≤ 0.05) toward complete oxidation relative to non-exercisers. MSCs from offspring of all exercising mothers also had lower rates of incomplete fatty acid oxidation (P ≤ 0.05), which was related to infant adiposity at 1 month of age. MSCs from all exercising groups exhibited higher insulin-stimulated glycogen synthesis rates (P ≤ 0.05), with RE having the largest effect (P ≤ 0.05). RE also had the greatest effect on MSC glucose oxidation rates (P ≤ 0.05) and partitioning toward complete oxidation (P ≤ 0.05). CONCLUSION: Our data demonstrates that maternal exercise enhances glucose and lipid metabolism of offspring MSCs. Improvements in MSC glucose metabolism seem to be the greatest with maternal RE. Clinical Trial: ClinicalTrials.gov Identifier: NCT03838146.
Subject(s)
Glucose , Mesenchymal Stem Cells , Pregnancy , Humans , Female , Glucose/metabolism , Lipid Metabolism , Obesity/metabolism , Fatty Acids/metabolismABSTRACT
Women with overweight or obesity (OWOB) have an increased risk of cesarean birth, preterm birth (PTB), and high birth weight infants. Although regular exercise decreases this risk in healthy weight women, these associations have not been explored in OWOB. Women were randomized at 13-16 weeks' gestation to 150-min of moderate-intensity exercise (n = 131) or non-exercising control (n = 61). Delivery mode, gestational age (GA), and birth weight (BW) were obtained via electronic health records. Pregnant exercisers had no differences in risk of cesarean birth, PTB, or BW compared to control participants. OWOB exercisers had higher rates of cesarean birth (27.1% vs. 11.1%), trends of higher PTB (15.3% vs. 5.6%), but normal weight babies relative to normal weight exercisers. Controlling for race and body mass index (BMI), maternal exercise reduced the relative risk (RR) for cesarean birth from 1.63 to 1.43. Cesarean births predicted by pre-pregnancy BMI and fitness level, whereas BW was predicted by race, gestational weight gain (GWG), pre-pregnancy fitness level, and exercise level. Cesarean birth was predicted by pre-pregnancy BMI and fitness level, while maternal exercise reduced the magnitudes of the relative risks of cesarean birth. Maternal exercise, pre-pregnancy fitness level, and GWG predict neonatal BW.Trial Registration: Influence of Maternal Exercise on Infant Skeletal Muscle and Metabolomics-#NCT03838146, 12/02/2019, https://register.clinicaltrials.gov/prs/app/template/EditRecord.vm?epmode=Edit&listmode=Edit&uid=U0003Z0X&ts=8&sid=S0008FWJ&cx=77ud1i .
Subject(s)
Exercise Therapy , Obesity, Maternal , Prenatal Care , Birth Weight , Body Mass Index , Cesarean Section/statistics & numerical data , Exercise Therapy/methods , Female , Humans , Infant, Newborn , Obesity, Maternal/epidemiology , Obesity, Maternal/therapy , Pregnancy , Premature Birth/epidemiology , Risk Assessment , Treatment OutcomeABSTRACT
African Americans (AA) are disproportionately burdened by metabolic diseases. While largely unexplored between Caucasian (C) and AA, differences in mitochondrial bioenergetics may provide crucial insight to mechanisms for increased susceptibility to metabolic diseases. AA display lower total energy expenditure and resting metabolic rate compared to C, but paradoxically have a higher amount of skeletal muscle mass, suggestive of inherent energetic efficiency differences between these races. Such adaptations would increase the chances of overnutrition in AA; however, these disparities would not explain the racial difference in insulin resistance (IR) in healthy subjects. Hallmarks associated with insulin resistance (IR), such as reduced mitochondrial oxidative capacity and metabolic inflexibility are present even in healthy AA without a metabolic disease. These adaptations might be influential of mitochondrial "substrate preference" and could play a role in disproportionate IR rates among races. A higher glycolytic flux and provision of shuttles transferring electrons from cytosol to mitochondrial matrix could be a contributing factor in development of IR via heightened reactive oxygen species (ROS) production. This review highlights the above concepts and provides suggestions for future studies that could help delineate molecular premises behind potential impairments in insulin signaling and metabolic disease susceptibility in AA.
ABSTRACT
Preclinical rodent and nonhuman primate models investigating maternal obesity have highlighted the importance of the intrauterine environment in the development of insulin resistance in offspring; however, it remains unclear if these findings can be translated to humans. To investigate possible intrauterine effects in humans, we isolated mesenchymal stem cells (MSCs) from the umbilical cord tissue of infants born to mothers of normal weight or mothers with obesity. Insulin-stimulated glycogen storage was determined in MSCs undergoing myogenesis in vitro. There was no difference in insulin action based on maternal obesity. However, maternal free fatty acid (FFA) concentration, cord leptin, and intracellular triglyceride content were positively correlated with insulin action. Furthermore, MSCs from offspring born to mothers with elevated FFAs displayed elevated activation of the mTOR signaling pathway. Taken together, these data suggest that infants born to mothers with elevated lipid availability have greater insulin action in MSCs, which may indicate upregulation of growth and lipid storage pathways during periods of maternal overnutrition.
Subject(s)
Mesenchymal Stem Cells , Obesity, Maternal , Animals , Fatty Acids, Nonesterified/metabolism , Female , Humans , Infant , Insulin/metabolism , Insulin, Regular, Human , Mesenchymal Stem Cells/metabolism , Obesity/metabolism , PregnancyABSTRACT
CONTEXT: Recent preclinical data suggest exercise during pregnancy can improve the metabolic phenotype not only of the mother, but of the developing offspring as well. However, investigations in human offspring are lacking. OBJECTIVE: To characterize the effect of maternal aerobic exercise on the metabolic phenotype of the offspring's mesenchymal stem cells (MSCs). DESIGN: Randomized controlled trial. SETTING: Clinical research facility. PATIENTS: Healthy female adults between 18 and 35 years of age andâ ≤â 16 weeks' gestation. INTERVENTION: Mothers were randomized into 1 of 2 groups: aerobic exercise (AE, nâ =â 10) or nonexercise control (CTRL, nâ =â 10). The AE group completed 150 minutes of weekly moderate-intensity exercise, according to American College of Sports Medicine guidelines, during pregnancy, whereas controls attended stretching sessions. MAIN OUTCOME MEASURES: Following delivery, MSCs were isolated from the umbilical cord of the offspring and metabolic tracer and immunoblotting experiments were completed in the undifferentiated (D0) or myogenically differentiated (D21) state. RESULTS: AE-MSCs at D0 had an elevated fold-change over basal in insulin-stimulated glycogen synthesis and reduced nonoxidized glucose metabolite (NOGM) production (Pâ ≤â 0.05). At D21, AE-MSCs had a significant elevation in glucose partitioning toward oxidation (oxidation/NOGM ratio) compared with CTRL (Pâ ≤â 0.05). Immunoblot analysis revealed elevated complex I expression in the AE-MSCs at D21 (Pâ ≤â 0.05). Basal and palmitate-stimulated lipid metabolism was similar between groups at D0 and D21. CONCLUSIONS: These data provide evidence of a programmed metabolic phenotype in human offspring with maternal AE during pregnancy.
Subject(s)
Glucose , Lipid Metabolism , Adult , Exercise , Female , Humans , Insulin , Pregnancy , Stem CellsABSTRACT
Epidemiological studies show that low birth weight is associated with mortality from cardiovascular disease in adulthood, indicating that chronic diseases could be influenced by hormonal or metabolic insults encountered in utero. This concept, now known as the Developmental Origins of Health and Disease hypothesis, postulates that the intrauterine environment may alter the structure and function of the organs of the fetus as well as the expression of genes that impart an increased vulnerability to chronic diseases later in life. Lifestyle interventions initiated during the prenatal period are crucial as there is the potential to attenuate progression towards chronic diseases. However, how lifestyle interventions such as physical activity directly affect human offspring metabolism and the potential mechanisms involved in regulating metabolic balance at the cellular level are not known. The purpose of this review is to highlight the effects of exercise during pregnancy on offspring metabolic health and emphasize gaps in the current human literature and suggestions for future research.
Subject(s)
Cardiovascular Diseases , Exercise , Adult , Female , Humans , Life Style , PregnancyABSTRACT
INTRODUCTION: Exercise usually results in less weight loss than expected. This suggests increased energy intake and/or deceased expenditure counteract the energy deficit induced by exercise. The aim of this study was to evaluate changes in components of daily energy expenditure (doubly labeled water and room calorimetry) after 24 wk of exercise training with two doses of aerobic exercise. METHODS: This was an ancillary study in 42 (29 women, 13 men) sedentary, middle-age (47.8 ± 12.5 yr) individuals with obesity (35 ± 3.7 kg·m-2) enrolled in the Examination of Mechanisms of Exercise-induced Weight Compensation study. Subjects were randomized to three groups: healthy living control group (n = 13), aerobic exercise that expended 8 kcal·kg-1 of body weight per week (8 KKW, n = 14), or aerobic exercise that expended 20 kcal per kilogram of weight per week (20 KKW, n = 15). Total daily energy expenditure (TDEE) was measured in free-living condition by doubly labeled water and in sedentary conditions in a metabolic chamber over 24 h (24EE). Energy intake was calculated over 14 d from TDEE before and after the intervention using the intake-balance method. RESULTS: Significant weight loss occurred with 20 KKW (-2.1 ± 0.7 kg, P = 0.04) but was only half of expected. In the 20 KKW group free-living TDEE increased by ~4% (P = 0.03), which is attributed to the increased exercise energy expenditure (P = 0.001), while 24EE in the chamber decreased by ~4% (P = 0.04). Aerobic exercise at 8 KKW did not induce weight change, and there was no significant change in any component of EE. There was no significant change in energy intake for any group (P = 0.53). CONCLUSIONS: Structured aerobic exercise at a dose of 20 KKW produced less weight loss than expected possibly due to behavioral adaptations leading to reduced 24EE in a metabolic chamber without any change in energy intake.
Subject(s)
Energy Metabolism , Exercise Therapy/methods , Exercise/physiology , Obesity/therapy , Weight Loss/physiology , Adaptation, Physiological , Adult , Body Fat Distribution , Calorimetry, Indirect , Energy Intake , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Non-Hispanic black (NHB) pregnant women disproportionately experience adverse birth outcomes compared to Non-Hispanic white (NHW) pregnant women. The positive effects of prenatal exercise on maternal and neonatal health may mitigate these disparities. This study evaluated the influence of prenatal exercise on racial/ethnic disparities in gestational age (GA), birthweight (BW), and risks of preterm birth (PTB), cesarean section (CS), and low-birthweight (LBW) neonates. METHODS: This study performed a secondary data analysis using data from a 24-week, two-arm exercise intervention trial (ENHANCED by Mom). Women with singleton pregnancies (< 16 weeks), aged 18-40 years, BMI between 18.5-34.99 kg/m2, and no preexisting health conditions were eligible. The aerobic exercisers (EX) participated in 150 min of moderate-intensity weekly exercise while non-exercising controls (CON) attended low-intensity stretching/breathing sessions. Data on GA, PTB (< 37 weeks), BW, LBW (< 2.5 kg), and delivery mode were collected. Poisson, median and linear regressions were performed. RESULTS: Participants with complete data (n = 125) were eligible for analyses (EX: n = 58, CON: n = 67). NHB pregnant women delivered lighter neonates (ß = - 0.43 kg, 95% CI: - 0.68, - 0.18, p = 0.001). After adjusting for prenatal exercise, racial/ethnic disparities in BW were reduced (ß = - 0.39 kg, 95% CI: - 0.65, - 0.13, p = 0.004). Prenatal exercise reduced borderline significant racial/ethnic disparities in PTB (p = 0.053) and GA (p = 0.07) with no effects found for CS and LBW. CONCLUSIONS: The findings of this study demonstrate that prenatal exercise may attenuate the racial/ethnic disparities observed in neonatal BW, and possibly GA and PTB. Larger, diverse samples and inclusion of maternal biomarkers (e.g., cytokines) are encouraged to further evaluate these relationships.
Subject(s)
Black or African American/statistics & numerical data , Exercise Therapy/methods , Health Status Disparities , Premature Birth/epidemiology , White People/statistics & numerical data , Adolescent , Adult , Cesarean Section/statistics & numerical data , Female , Humans , Infant Health , Infant, Low Birth Weight , Infant, Newborn , Pregnancy , Premature Birth/prevention & control , Treatment Outcome , Young AdultABSTRACT
Fasting plasma lactate concentrations are elevated in individuals with metabolic disease. The aim of this study was to determine if the variance in fasting lactate concentrations were associated with factors linked with cardiometabolic health even in a young, lean cohort. Young (age 22 ± 0.5; N = 30) lean (BMI (22.4 ± 0.4 kg/m2 ) women were assessed for waist-to-hip ratio, aerobic capacity (VO2 peak), skeletal muscle oxidative capacity (near infrared spectroscopy; fat oxidation from muscle biopsies), and fasting glucose and insulin (HOMA-IR). Subjects had a mean fasting lactate of 0.9 ± 0.1 mmol/L. The rate of deoxygenation of hemoglobin/myoglobin (R2 = .23, p = .03) in resting muscle and skeletal muscle homogenate fatty acid oxidation (R2 = .72, p = .004) were inversely associated with fasting lactate. Likewise, cardiorespiratory fitness (time to exhaustion during the VO2 peak test) was inversely associated with lactate (R2 = .20, p = .05). Lactate concentration was inversely correlated with HDL:LDL (R2 = .57, p = .02) and positively correlated with the waist to hip ratio (R2 = .52, p = .02). Plasma lactate was associated with various indices of cardiometabolic health. Thus, early determination of fasting lactate concentration could become a common biomarker used for identifying individuals at early risk for metabolic diseases.
Subject(s)
Cardiorespiratory Fitness , Energy Metabolism , Lactic Acid/blood , Metabolic Diseases/diagnosis , Mitochondria, Muscle/metabolism , Muscle Contraction , Quadriceps Muscle/metabolism , Biomarkers/blood , Cardiometabolic Risk Factors , Female , Health Status , Healthy Volunteers , Humans , Metabolic Diseases/blood , Metabolic Diseases/physiopathology , Predictive Value of Tests , Risk Assessment , Young AdultABSTRACT
The birth rates among women of advanced maternal age (AMA) have risen over the last two decades; yet, pregnancies with AMA are considered high-risk and are associated with a significant increase in pregnancy complications. Although the mechanisms leading to pregnancy complications in women with AMA are not fully understood, it has been well established in the literature that offspring exposed to unfavorable environmental conditions in utero, such as gestational diabetes, preeclampsia, and/or intrauterine growth restriction during the early stages of development are subject to long-term health consequences. Additionally, angiogenic growth mediators, which drive vascular development of the placenta, are imbalanced in pregnancies with AMA. These same imbalances also occur in pregnancies complicated by preeclampsia, gestational diabetes, and obesity. This review discusses the impact of AMA on pregnancy and offspring health, and the potential mechanistic role of placental angiogenic growth mediators in the development of pregnancy complications at AMA.
Subject(s)
Maternal Age , Maternal Health , Placenta/metabolism , Female , Fetal Growth Retardation/metabolism , Fetal Growth Retardation/physiopathology , Humans , Placenta/blood supply , Placenta/physiopathology , PregnancyABSTRACT
BACKGROUND: Optimal maternal metabolism during pregnancy is essential for healthy fetal growth and development. Chronic exercise is shown to positively affect metabolism, predominantly demonstrated in nonpregnant populations. OBJECTIVE: To determine the effects of aerobic exercise on maternal metabolic biomarkers during pregnancy, with expected lower levels of glucose, insulin, and lipids among exercise-trained pregnant women. METHODS: Secondary data analyses were performed using data from two, longitudinal prenatal exercise intervention studies (ENHANCED by MOM and GESTAFIT). Exercisers completed 150 min of weekly moderate-intensity exercise during pregnancy (24+ weeks) while nonexercisers attended stretching sessions. Pregnant women were 31-33 years of age, predominantly non-Hispanic white, and "normal weight" body mass index. At 16 and 36 weeks of gestation, fasting blood samples were collected via fingerstick and venipuncture. Maternal glucose, insulin, insulin resistance (HOMA-IR), total cholesterol (TC), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triglycerides (TG) were analyzed. ANCOVA analyses were performed to evaluate the effects of aerobic exercise on markers of maternal metabolism in late pregnancy, controlling for baseline levels. RESULTS: Our sample included 12 aerobic exercisers and 54 nonexercising control groups. Significant between-groups differences at 16 weeks of gestation were found for TG (92.3 vs. 121.2 mg/dl, p = .04), TC (186.8 vs. 219.6 mg/dl, p = .002), and LDL (104.1 vs. 128.8 mg/dl, p = .002). Aerobic-trained pregnant women exhibited lower insulin levels in late pregnancy (ß = -2.6 µIU/ml, 95% CI:-4.2, -0.95, p = .002) and a reduced increase in insulin levels from 16 to 36 week of gestation (ß = -2.3 µIU/ml, 95% CI: -4.4, -0.2, p = .034) compared with nonexercising pregnant women. No statistically significant effects were observed for maternal HOMA-IR, TC, LDL, HDL, TC:HDL, and TG in late pregnancy. CONCLUSIONS: The observations of this study demonstrate that prenatal exercise may positively affect maternal insulin, with aerobic-trained pregnant women exhibiting lower insulin levels in late pregnancy. Additionally, we found no appreciable effects of prenatal exercise on maternal lipids in late pregnancy.
Subject(s)
Exercise , Insulin , Biomarkers , Female , Humans , Lipids , Pregnancy , TriglyceridesABSTRACT
This prospective, observational study investigated changes in sleep and the effect on energy intake, gestational weight gain, and cardiometabolic health across pregnancy in 52 healthy pregnant women with obesity. Habitual sleep was assessed by wrist-worn actigraphy (time spent in bed; TIB, total sleep time; TST, and sleep efficiency) in early (130-156 weeks) and late (350-366) pregnancy. A change to habitual sleep was defined as change of one-half of the standard deviation of TIB and TST across six consecutive nights from early pregnancy. Energy intake and changes in weight, fasting glucose, insulin, and lipids across pregnancy were compared between women who changed sleep. During early pregnancy, TIB was 9:24 ± 0:08 h and varied by 1:37 ± 0:07 h across the six nights. TST and sleep efficiency significantly declined from early to late pregnancy (7:03 ± 0:08 h to 6:28 ± 0:09 h, p < 0.001) and (76 ± 0.1% to 71 ± 0.2%, p < 0.001), respectively. For women who increased TIB (n = 11), fasting glucose decreased (-11.6 ± 4.3%, p < 0.01) across pregnancy and they had a trend towards decreased insulin (-57.8 ± 33.5%; p = 0.09) and HOMA-IR (-72.4 ± 37.3%; p = 0.06) compared to women who decreased TIB (n = 13). Women who increased TIB had a significantly lower daily energy intake across pregnancy (-540 ± 163 kcal; p < 0.01) and tended to have less gestational weight gain (-147 ± 88 g/week; p = 0.10). Changes in TST did not affect plasma markers, energy intake or weight gain. The positive relationship between sleep and cardiometabolic health during pregnancy is explained in part by lower energy intake. We hypothesize lower energy intake is due to a prolonged overnight fast and a decrease in the time available for eating.
Subject(s)
Cardiovascular Diseases , Energy Intake , Female , Humans , Obesity , Pregnancy , Prospective Studies , SleepABSTRACT
INTRODUCTION: A key component to analyzing wearable sensor data is identifying periods of non-wear. Traditionally, strings of consecutive zero counts (e.g. >60-minutes) are identified indicating periods of non-movement. The non-movement window length is then evaluated as wear or non-wear. Given that non-movement is not equivalent to non-wear, additional criteria should be evaluated to objectively identify periods of non-wear. Identifying non-wear is especially challenging in infants due to their sporadic movement, sleep frequency, and proportion of caregiver-generated movement. PURPOSE: To use hip- and ankle-worn ActiGraph wGT3X-BT (wGT3X-BT) data to identify non-wear in infants. METHODS: Fifteen infant participants [mean±SD; age, 8.7±1.7 weeks (range 5.4-11.3 weeks); 5.1±0.8 kg; 56.2±2.1 cm; n = 8 females] wore a wGT3X-BT on the hip and ankle. Criterion data were collected during two, 2-hour directly observed periods in the laboratory. Using raw 30 Hz acceleration data, a vector magnitude and the inclination angle of each individual axis were calculated before being averaged into 1-minute windows. Three decision tree models were developed using data from 1) hip only, 2) ankle only, and 3) hip and ankle combined. RESULTS: The hip model classified 86.6% of all minutes (wear and non-wear) correctly (F1 = 75.5%) compared to the ankle model which classified 90.6% of all minutes correctly (F1 = 83.0%). The combined site model performed similarly to the ankle model and correctly classified 90.0% of all minutes (F1 = 80.8%). CONCLUSION: The similar performance between the ankle only model and the combined site model likely indicates that the features from the ankle device are more important for identifying non-wear in infants. Overall, this approach provides an advancement in the identification of device wear status using wearable sensor data in infants.