ABSTRACT
High cardiorespiratory fitness (CRF) is associated with a reduced risk of metabolic disease and is linked to superior mitochondrial respiratory function. This study investigated how intrinsic CRF affects bioenergetics and metabolic health in adulthood and early life. Adult rats selectively bred for low and high running capacity [low capacity runners (LCR) and high capacity runners (HCR), respectively] underwent metabolic phenotyping before mating. Weanlings were evaluated at 4-6 wk of age, and whole body energetics and behavior were assessed using metabolic cages. Mitochondrial respiratory function was assessed in permeabilized tissues through high-resolution respirometry. Proteomic signatures of adult and weanling tissues were determined using mass spectrometry. The adult HCR group exhibited lower body mass, improved glucose tolerance, and greater physical activity compared with the LCR group. The adult HCR group demonstrated higher mitochondrial respiratory capacities in the soleus and heart compared with the adult LCR group, which coincided with a greater abundance of proteins involved in lipid catabolism. HCR and LCR weanlings had similar body mass, but HCR weanlings displayed reduced adiposity. In addition, HCR weanlings exhibited better glucose tolerance and higher physical activity levels than LCR weanlings. Higher respiratory capacities were observed in the soleus, heart, and liver tissues of HCR weanlings compared with LCR weanlings, which were not owed to greater mitochondrial content. Proteomic analyses indicated a greater potential for lipid oxidation in the contractile muscles of HCR weanlings. In conclusion, offspring born to parents with high CRF possess an enhanced capacity for lipid catabolism and oxidative phosphorylation, thereby influencing metabolic health. These findings highlight that intrinsic CRF shapes the bioenergetic phenotype with implications for metabolic resilience in early life.NEW & NOTEWORTHY Inherited cardiorespiratory fitness (CRF) influences early life bioenergetics and metabolic health. Higher intrinsic CRF was associated with reduced adiposity and improved glucose tolerance in early life. This metabolic phenotype was accompanied by greater mitochondrial respiratory capacity in skeletal muscle, heart, and liver tissue. Proteomic profiling of these three tissues further revealed potential mechanisms linking inherited CRF to early life metabolism.
Subject(s)
Cardiorespiratory Fitness , Physical Conditioning, Animal , Rats , Animals , Proteomics , Liver/metabolism , Lipids , Glucose/metabolism , Physical Conditioning, Animal/physiologyABSTRACT
BACKGROUND: Rodent models suggest that in utero exposure to under and overnutrition programs offspring physical activity (PA) behaviors. Such nexus has not been established in humans. This study evaluated the association of early pregnancy maternal adiposity with offspring PA at age 2 years (2-yo-PA) taking into consideration prenatal and postnatal factors. METHODS: Women (n = 153) were enrolled early in pregnancy (<10 weeks). At enrollment, maternal adiposity [air displacement plethysmography, fat mass index (FMI, kg/m2)] and PA (accelerometers, activity counts) were measured, and age, race, and education self-reported. Gestational weight gain was measured at the research facility. Offspring birthweight and sex were self-reported. At age 2 years, parental feeding practices (child feeding questionnaire) were assessed, whereas anthropometrics (length and weight) and physical activity (accelerometers) were objectively measured. Offspring body mass index z-scores were calculated. Generalized linear regression analysis modeled the association of maternal FMI and 2-yo-PA [average activity counts (AC)4/day]. RESULTS: In bivariate associations, 2-yo-PA did not associate with maternal FMI (ß = -0.22, CI = -0.73 to 0.29, p = 0.398). However, maternal FMI interacted with offspring sex in association with 2-yo-PA. Specifically, 2-yo-PA was lower in girls (ß = -1.14, CI = -2.1 to -0.18, p = 0.02) compared to boys when maternal FMI was ≥7 kg/m2. When stratified by sex, 2-yo-PA of girls negatively associated with maternal FMI (ß = -0.82, CI = -1.43 to 0.29, p = 0.009) while no association was found between maternal FMI and boy's PA (ß = 0.32, CI = -0.38 to 1.01, p = 0.376). CONCLUSIONS: The association of 2-yo-PA and early pregnancy maternal adiposity was modified by offspring sex. Offspring's physical activity decreased with increasing early pregnancy adiposity maternal in girls but not boys in second parity dyads.
Subject(s)
Adiposity , Obesity, Maternal , Male , Child , Pregnancy , Humans , Female , Child, Preschool , Obesity , Body Mass Index , Exercise , AnthropometryABSTRACT
BACKGROUND: Digital interventions are increasingly used to improve health behaviors. Improved access and lower costs (relative to in-person interventions) make such interventions appealing. Specifically, digital platforms may be a promising approach for increasing physical activity (PA) in young children. OBJECTIVE: The goal of this systematic review was three-pronged: (1) to determine the quality of studies using digital PA intervention strategies with preschool-aged children (ie, 3 to 5 years old); (2) to assess the efficacy of digital interventions and approaches designed to improve PA in preschool-aged children; and (3) to examine theoretical application and implementation outcomes with current approaches to digital PA interventions. METHODS: This review identified and summarized studies on digitally supported interventions for promoting PA in preschool-aged children. We generated 3 lists of relevant search terms that included technology-related terms, PA-related terms, and weight-related terms. The search included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Study selection was led by a single author and verified by a second; the same 2 authors assessed study quality using a standardized tool, and 3 authors completed data extraction on PA outcomes, theory application, and implementation outcomes. RESULTS: In total, 601 studies were identified; 8 met the inclusion criteria. For study quality, only 2 studies received an overall rating of strong quality and low risk of bias. All but 1 study had a small sample size (<100). Positive and significant changes in child PA outcomes were reported in only 2 studies with weak overall quality, both of which used child-directed approaches. In total, 5 studies applied a behavioral theory for designing the intervention; no patterns of effectiveness were identified based on the application of theory. Finally, no studies reported on the implementation outcomes of adoption, cost, penetration, or sustainability; 1 study did not assess any implementation outcomes, and no single study reported on more than 2 implementation outcomes. Studies measured the implementation outcome of acceptability most frequently (n=4), and researchers assessed fidelity in 3 studies. CONCLUSIONS: The interventions with a significant effect on PA used child-centered activities; parent-directed digital interventions alone were ineffective for improving PA. Future research with rigorous designs, monitoring of implementation outcomes, and testing of the contributions of digital components will advance understanding of the effectiveness of digital interventions for increasing PA in children.
Subject(s)
Health Behavior , Parents , Child, Preschool , Exercise , HumansABSTRACT
BACKGROUND: We report the design, protocol and statistical analysis plan for the Arkansas Active Kids (AAK) Study. The study investigates the complex relationships between factors that contribute to metabolic health and obesity status in prepubertal school-age children in the state of Arkansas. AIM: We aim to identify modifiable behavioral and environmental factors and phenotypes related to metabolic health that are associated with obesity status that, if addressed effectively, can aid in designing effective intervention strategies to improve fitness and reduce obesity in children. METHODS: We analyzed dietary and physical activity data from two national surveys (National Survey of Children's Health and Youth Risk Behavior Surveillance System). We then conducted detailed surveys to collect dietary, physical activity, socio-demographic, and environmental data from a sample of 226 prepubertal Arkansas children. In the same sample of prepubertal children, we also collected extensive physiologic data to further study associations between physical activity and metabolic health. RESULTS: All study visits included detailed measures of vital signs, energy expenditure, components of physical fitness, body composition and the collection of biological samples for determination of metabolic analytes. CONCLUSION: The observational, environmental and physiological results will be used to craft multivariate statistical models to identify which variables define 'phenotype signatures' that associate with fitness level and obesity status.
Subject(s)
Pediatric Obesity , Adolescent , Arkansas , Child , Exercise , Humans , Pediatric Obesity/epidemiology , Pediatric Obesity/prevention & control , Physical Fitness , SchoolsABSTRACT
BACKGROUND: Branched-chain amino acid (BCAA) concentrations in the blood have been correlated with insulin resistance, but this relation throughout gestation (period in which insulin resistance typically increases) is unclear. OBJECTIVE: The objective of this study was to determine the associations between changes in BCAA concentrations and estimates of insulin resistance throughout gestation. METHODS: Serum BCAA (Leu, Ile, Val) concentrations and insulin resistance/sensitivity [i.e., homeostatic model assessment-2 of insulin resistance (HOMA2-IR), estimated metabolic clearance rate (MCR) of glucose, and estimated first- and second-phase insulin responses] were assessed at early (EP; 8.5 ± 0.2 wk) and/or late (LP; 29.2 ± 0.8 wk) pregnancy in 53 healthy women from the Glowing cohort. Adjusted Spearman correlations were used to evaluate the association between BCAA and insulin resistance/sensitivity measures at EP and LP, adjusted for body fat percentage and gestational weight gain (GWG). A multiple linear regression analysis was used to assess the association between changes in HOMA2-IR and BCAAs throughout gestation. Groups were made post hoc based on the mean percentage change (10% decrease) in Leu throughout gestation, creating a group with a ≥10% decrease in LeuLP-EP (BELOW) and a <10% decrease in LeuLP-EP (ABOVE), and Student's t tests were performed to assess differences between groups. RESULTS: Leu and Ile concentrations positively correlated with HOMA2-IR at both time points, but these relations at EP disappeared/weakened when adjusted for body fat percentage. From EP to LP, the change in Leu (LeuLP-EP) was negatively associated with the change in HOMA2-IR (HOMA2-IRLP-EP) (ß = -0.037, P = 0.006). MCR was lower in the BELOW group compared with the ABOVE group, whereas there was no difference in HOMA2-IR between groups. CONCLUSIONS: In this pregnancy cohort, BCAA concentrations decreased throughout gestation, whereas the mean insulin resistance did not change. These data do not support a connection between changes in blood BCAA concentrations and estimates of insulin resistance in pregnant women. This trial is registered at clinicaltrials.gov as NCT01131117.
Subject(s)
Amino Acids, Branched-Chain/blood , Insulin Resistance , Adult , Cohort Studies , Female , Humans , PregnancyABSTRACT
Skeletal muscle mitochondrial respiration is thought to be altered in obesity, insulin resistance, and type 2 diabetes; however, the invasive nature of tissue biopsies is an important limiting factor for studying mitochondrial function. Recent findings suggest that bioenergetics profiling of circulating cells may inform on mitochondrial function in other tissues in lieu of biopsies. Thus, we sought to determine whether mitochondrial respiration in circulating cells [peripheral blood mononuclear cells (PBMCs) and platelets] reflects that of skeletal muscle fibers derived from the same subjects. PBMCs, platelets, and skeletal muscle (vastus lateralis) samples were obtained from 32 young (25-35 yr) women of varying body mass indexes. With the use of extracellular flux analysis and high-resolution respirometry, mitochondrial respiration was measured in intact blood cells as well as in permeabilized cells and permeabilized muscle fibers. Respiratory parameters were not correlated between permeabilized muscle fibers and intact PBMCs or platelets. In a subset of samples (n = 12-13) with permeabilized blood cells available, raw measures of substrate (pyruvate, malate, glutamate, and succinate)-driven respiration did not correlate between permeabilized muscle (per mg tissue) and permeabilized PBMCs (per 106 cells); however, complex I leak and oxidative phosphorylation coupling efficiency correlated between permeabilized platelets and muscle (Spearman's ρ = 0.64, P = 0.030; Spearman's ρ = 0.72, P = 0.010, respectively). Our data indicate that bioenergetics phenotypes in circulating cells cannot recapitulate muscle mitochondrial function. Select circulating cell bioenergetics phenotypes may possibly inform on overall metabolic health, but this postulate awaits validation in cohorts spanning a larger range of insulin resistance and type 2 diabetes status.
Subject(s)
Blood Cells/metabolism , Mitochondria, Muscle/metabolism , Muscle Fibers, Skeletal/metabolism , Oxygen Consumption/physiology , Adult , Blood Glucose/analysis , Blood Platelets/metabolism , Body Mass Index , Energy Metabolism/physiology , Female , Humans , Insulin/blood , Monocytes/metabolism , Muscle, Skeletal/metabolism , Oxidative Phosphorylation Coupling Factors/metabolism , Triglycerides/bloodABSTRACT
The effects of amino acid supply and insulin infusion on skin protein kinetics (fractional synthesis rate (FSR), fractional breakdown rate (FBR), and net balance (NB)) in pigs were investigated. Four-month-old pigs were divided into four groups as follows: control, insulin (INS), amino acid (AA), and INS + AA groups based on the nutritional and hormonal conditions. l-[ring-(13)C6]Phenylalanine was infused. FBR was estimated from the enrichment ratio of arterial phenylalanine to intracellular free phenylalanine. Plasma INS was increased (p < 0.05) in the INS and INS + AA groups. Plasma glucose was maintained by infusion of glucose in the groups receiving INS. The interventions did not change the NB of skin protein. However, the interventions affected the FSR and FBR differently. An infusion of INS significantly increased both FSR and FBR, although AA infusion did not. When an AA infusion was added to the infusion of insulin (INS + AA group), FSR and FBR were both lower when compared with the INS group. Our data demonstrate that in anesthetized pigs INS infusion did not exert an anabolic effect, but rather it increased AA cycling into and out of skin protein. Because co-infusion of AAs with INS ameliorated this effect, it is likely that the increased AA cycling during INS infusion was related to AA supply. Although protein kinetics were affected by both INS and AAs, none of the interventions affected the skin protein deposition. Thus, skin protein content is closely regulated under normal circumstances and is not subject to transient changes in AAs or hormonal concentrations.
Subject(s)
Amino Acids/metabolism , Hyperinsulinism/metabolism , Hyperinsulinism/veterinary , Skin/metabolism , Swine/metabolism , Animals , Female , Hyperinsulinism/physiopathology , Skin/physiopathologyABSTRACT
Mitochondrial health is critical to physiological function, particularly in tissues with high ATP turnover, such as striated muscle. It has been postulated that derangements in skeletal muscle mitochondrial function contribute to impaired physical function in older adults. Here, we determined mitochondrial respiratory capacity and coupling control in skeletal muscle biopsies obtained from young and older adults. Twenty-four young (28 ± 7 yr) and thirty-one older (62 ± 8 yr) adults were studied. Mitochondrial respiration was determined in permeabilized myofibers from the vastus lateralis after the addition of substrates oligomycin and CCCP. Thereafter, mitochondrial coupling control was calculated. Maximal coupled respiration (respiration linked to ATP production) was lower in muscle from older vs. young subjects (P < 0.01), as was maximal uncoupled respiration (P = 0.06). Coupling control in response to the ATP synthase inhibitor oligomycin was lower in older adults (P < 0.05), as was the mitochondria flux control ratio, coupled respiration normalized to maximal uncoupled respiration (P < 0.05). Calculation of respiratory function revealed lower respiration linked to ATP production (P < 0.001) and greater reserve respiration (P < 0.01); i.e., respiratory capacity not used for phosphorylation in muscle from older adults. We conclude that skeletal muscle mitochondrial respiratory capacity and coupling control decline with age. Lower respiratory capacity and coupling efficiency result in a reduced capacity for ATP production in skeletal muscle of older adults.
Subject(s)
Aging , Down-Regulation , Electron Transport Complex II/metabolism , Electron Transport Complex I/metabolism , Mitochondria, Muscle/metabolism , Muscle, Skeletal/growth & development , Oxidative Phosphorylation , Adult , Aged , Aged, 80 and over , Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology , Cohort Studies , Down-Regulation/drug effects , Electron Transport Complex I/antagonists & inhibitors , Electron Transport Complex II/antagonists & inhibitors , Female , Humans , Male , Middle Aged , Mitochondria, Muscle/drug effects , Mitochondria, Muscle/enzymology , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Myofibrils/drug effects , Myofibrils/enzymology , Myofibrils/metabolism , Oligomycins/pharmacology , Oxidative Phosphorylation/drug effects , Proton Ionophores/pharmacology , Quadriceps Muscle/drug effects , Quadriceps Muscle/growth & development , Quadriceps Muscle/metabolism , Uncoupling Agents/pharmacology , Young AdultABSTRACT
Elevated metabolic rate is a hallmark of the stress response to severe burn injury. This response is mediated in part by adrenergic stress and is responsive to changes in ambient temperature. We hypothesize that uncoupling of oxidative phosphorylation in skeletal muscle mitochondria contributes to increased metabolic rate in burn survivors. Here, we determined skeletal muscle mitochondrial function in healthy and severely burned adults. Indirect calorimetry was used to estimate metabolic rate in burn patients. Quadriceps muscle biopsies were collected on two separate occasions (11 ± 5 and 21 ± 8 days postinjury) from six severely burned adults (68 ± 19% of total body surface area burned) and 12 healthy adults. Leak, coupled, and uncoupled mitochondrial respiration was determined in permeabilized myofiber bundles. Metabolic rate was significantly greater than predicted values for burn patients at both time points (P < 0.05). Skeletal muscle oxidative capacity, citrate synthase activity, a marker of mitochondrial abundance, and mitochondrial sensitivity to oligomycin were all lower in burn patients vs. controls at both time points (P < 0.05). A greater proportion of maximal mitochondrial respiration was linked to thermogenesis in burn patients compared with controls (P < 0.05). Increased metabolic rate in severely burned adults is accompanied by derangements in skeletal muscle mitochondrial function. Skeletal muscle mitochondria from burn victims are more uncoupled, indicating greater heat production within skeletal muscle. Our findings suggest that skeletal muscle mitochondrial dysfunction contributes to increased metabolic rate in burn victims.
Subject(s)
Burns/complications , Burns/metabolism , Mitochondria, Muscle/physiology , Mitochondrial Diseases/etiology , Muscle, Skeletal/metabolism , Adult , Basal Metabolism , Biopsy , Burns/pathology , Case-Control Studies , Cell Respiration , Humans , Male , Middle Aged , Mitochondrial Diseases/metabolism , Mitochondrial Diseases/pathology , Muscle, Skeletal/pathology , Muscle, Skeletal/ultrastructure , Rest , Severity of Illness Index , Young AdultABSTRACT
INTRODUCTION: Clustering of cardiometabolic risk factors in childhood significantly increases the risk of atherosclerotic cardiovascular disease later in life. Identification of modifiable parental factors that contribute to offspring cardiometabolic health is critical for the prevention of disease. The objective was to identify factors associated with child cardiometabolic risk factors at age 5 years. METHODS: Triads from a longitudinal cohort were recalled at 5 years (n = 68). Dietary intake, anthropometrics, physical activity and serum-based risk factors were collected. Best subset selection, linear and logistic regressions were used to identify triad variables associated with increased risk of cardiometabolic risk factor clustering at age 5 years. RESULTS: In this cohort, best subset modelling revealed that increased paternal fat mass, serum low-density lipoproteins and triglycerides, maternal dietary added sugar and being female were associated with increased odds of offspring having two or more cardiometabolic risk factors at age 5 years. CONCLUSIONS: Dietary and exercise interventions prior to conception targeting paternal adiposity and dyslipidaemia as well as maternal dietary habits could decrease children's cardiometabolic risk in later life.
ABSTRACT
Context: Steatotic liver disease is common but overlooked in childhood obesity; diagnostic methods are invasive or expensive. Objective: We sought to determine the diagnostic accuracy of vibration-controlled transient elastography (VCTE) compared with magnetic resonance imaging (MRI) in adolescents with obesity and high risk for hepatosteatosis. Methods: Baseline data in 3 clinical trials enrolling adolescents with obesity were included (NCT03919929, NCT03717935, NCT04342390). Liver fat was assessed using MRI fat fraction and VCTE-based controlled attenuation parameter (CAP). Hepatosteatosis was defined as MRI fat fraction ≥5.0%. The area under the receiver-operating characteristic curves (AUROCs) for CAP against MRI was calculated, and optimal CAP using the Youden index for hepatosteatosis diagnosis was determined. Results: Data from 82 adolescents (age 15.6 ± 1.4 years, body mass index 36.5 ± 5.9 kg/m2, 81% female) were included. Fifty youth had hepatosteatosis by MRI (fat fraction 9.3% ; 95% CI 6.7, 14.0), and 32 participants did not have hepatosteatosis (fat fraction 3.1%; 95% CI 2.2, 3.9; P < .001). The hepatosteatosis group had higher mean CAP compared with no hepatosteatosis (293 dB/m; 95% CI 267, 325 vs 267 dB/m; 95% CI 248, 282; P = .0120). A CAP of 281 dB/m had the highest sensitivity (60%) and specificity (74%) with AUROC of 0.649 (95% CI 0.51-0.79; P = .04) in the entire cohort. In a subset of participants with polycystic ovary syndrome (PCOS), a CAP of 306 dB/m had the highest sensitivity (78%) and specificity (52%) and AUROC of 0.678 (95% CI 0.45-0.90; P = .108). Conclusion: CAP of 281 dB/m has modest diagnostic performance for hepatosteatosis compared with MRI in youth with significant obesity. A higher CAP in youth with PCOS suggests that comorbidities might affect optimal CAP in hepatosteatosis diagnosis.
ABSTRACT
Noninvasive cardiopulmonary exercise testing (CPET) provides the valuable capacity to analyze pulmonary gas exchange and cardiovascular responses that can be used to differentiate normal cardiopulmonary responses from abnormal. This case report highlights a proposed role for CPET in identifying potential cardiac pathologies in at-risk adolescents. An abnormal CPET response in an asymptomatic adolescent revealed a family history of early-age CAD. The significance of the abnormal CPET response was further supported by the presence of an elevated concentration of circulating high sensitivity C-reactive protein (hs-CRP). These findings emphasize the importance of a thorough clinical evaluation in at-risk adolescents, as CPET can aid in the early detection and management of cardiac pathologies, especially when combined with other relevant biomarkers such as plasma hs-CRP concentration, which can further suggest underlying pathology. Management considerations using serial CPET evaluations are recommended. Thus, CPET abnormalities combined with elevated hs-CRP should be taken seriously and provide justification for further evaluation and monitoring in adolescents at risk for cardiovascular disease.
ABSTRACT
The health benefits of soy foods are attributed to the high-quality protein and the bioactive compounds such as isoflavones. We previously reported that feeding obese (fa/fa) Zucker rats soy protein concentrates (SPCs) with low isoflavone (LIF) and high isoflavone (HIF) for 9 weeks significantly reduced liver steatosis compared to a casein control (C) diet. The current study extended the dietary treatments to 18 weeks to investigate the long-term effect of LIF and HIF SPC diets. 6-week-old male lean (L, n = 21) and obese (O, n = 21) Zucker rats were fed a casein C diet, LIF and HIF SPC diets for 18 weeks and body weight (BW) was recorded twice weekly. Rats were killed after 18 weeks to measure liver steatosis and serum aspartate aminotransferase and alanine aminotransferase. Obese rats had significantly greater final BW, liver weight, liver weight as the percentage of BW, and steatosis score compared to lean rats in all three dietary groups. The obese high-isoflavones (OHIF) group had significantly higher BW compared to obese control (OC) group (P < .0001) and obese low-isoflavones (OLIF) group (P = .01). OC group had significantly greater liver weight, liver weight as the percentage of BW, and liver steatosis score compared to OLIF (P = .0077, P < .0001 and P < .0001, respectively) and OHIF (P = .0094, P < .0001, and P < .0001, respectively) groups. Taken together, long-term feeding of SPC diets protected against liver steatosis regardless of isoflavone levels.
Subject(s)
Fatty Liver , Isoflavones , Male , Rats , Animals , Soybean Proteins , Caseins/pharmacology , Isoflavones/pharmacology , Rats, Zucker , Fatty Liver/prevention & control , Liver/metabolism , Obesity/metabolismABSTRACT
Background: Rodent models suggest that in utero exposure to under and overnutrition programs offspring physical activity (PA) behaviors. Such nexus has not been established in humans. This study evaluated the association of early pregnancy maternal adiposity with offspring PA at age 2 years (2-yo-PA) taking into consideration prenatal and postnatal factors. Methods: Women (n=153) were enrolled early in pregnancy (<10 weeks). At enrollment, maternal adiposity [air displacement plethysmography, fat mass index (FMI, kg/m2)] and PA (accelerometers, activity counts) were measured, and age, race, and education self-reported. Gestational weight gain was measured at the research facility. Offspring birthweight and sex were self-reported. At age 2 years, parental feeding practices (child feeding questionnaire) were assessed, whereas anthropometrics (length and weight) and physical activity (accelerometers) were objectively measured. Offspring body mass index z-scores were calculated. Generalized linear regression analysis modeled the association of maternal FMI and 2-yo-PA [average activity counts (AC)4/day]. Results: There was an interaction between maternal FMI and offspring sex in association with 2-yo-PA (ß= -1.03, p= 0.030). Specifically, 2-yo-PA was lower in girls compared to boys when maternal FMI was ≥7 kg/m2. Maternal PA early in pregnancy positively associated with 2-yo-PA (ß= 0.21, p= 0.005). In addition, children born to women with college education tended to be more active compared to children born to women without college education (ß= 3.46, p= 0.059). Conclusions: Sexual dimorphism was observed in the associations of maternal adiposity with 2-yo-PA, with girls being less active compared to boys only when maternal FMI was ≥7 kg/m2.
ABSTRACT
Purpose: To evaluate the association of platelet (PL) mitochondria respiration with markers of cardiovascular health in children ages 7-10 years. Methods: PL mitochondrial respiration (n = 91) was assessed by high resolution respirometry (HRR): Routine (R) respiration, complex (C) I linked respiration (CI), and maximal uncoupled electron transport capacity of CII (CIIE) were measured. The respiratory control ratio (RCR) was calculated as the ratio of maximal oxidative phosphorylation capacity of CI and CI leak respiration (PCI/LCI). Peak V Ë O2 (incremental bike test) and body composition (dual-energy X-ray absorptiometry) were measured. Multiple generalized linear regression analysis was used to model the association of measures by HRR with variables of interest: adiposity, low-density lipoprotein (LDL-C) and triglyceride (TG) status (normal vs. elevated) HOMA2-IR, blood pressure status (normal vs. high), and demographics. Results: R and CI-linked respiration positively associated with adiposity, high blood pressure (HBP), and peak V Ë O2. R and CI-linked respiration had inverse association with age and elevated LDL-C. CIIE was higher in children with elevated LDL-C (log-ß = -0.54, p = 0.010). HBP and peak V Ë O2 interacted in relation to RCR (log-ß = -0.01, p = 0.028). Specifically, RCR was lowest among children with HBP and low aerobic capacity (i.e., mean peak V Ë O2 -1SD). HOMA2-IR did not associate with measures of PL mitochondria respiration. Conclusion: In PL, R and CI-linked mitochondrial respiration directly associate with adiposity, peak V Ë O2 and HBP. Elevated LDL-C associates with lower CI-linked respiration which is compensated by increasing CII respiration. PL bioenergetics phenotypes in children associate with whole-body metabolic health status.
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AIMS: The increasing prevalence of childhood obesity escalates the risk for related complications. Circulating microRNAs (miRNAs) have been suggested as good predictive markers of insulin resistance in those with obesity. The aim was to identify a circulating miRNA profile that reflects insulin resistance in prepubertal children with obesity. MATERIAL AND METHODS: Plasma miRNAs were measured in prepubertal children (n = 63, 5-9 years) using TaqMan Advanced miRNA Human Serum/Plasma plates and then were validated by RT-qPCR. Subjects were divided into normal weight (n = 20, NW) and overweight or obese (n = 43, OW/OB) groups according to their BMI z-scores. The OW/OB group was further subdivided into insulin sensitive or metabolically healthy obese (n = 26, MHO) and insulin resistant or metabolically unhealthy obese (n = 17, MUO) according to HOMA-IR. KEY FINDINGS: While no differences were observed in the fasting plasma glucose levels, serum insulin levels were significantly elevated in the OW/OB compared to the NW group. Of 188 screened miRNAs, eleven were differentially expressed between the NW and OW/OB groups. Validation confirmed increased circulating levels of miR-146a-5p and miR-18a-5p in the OW/OB group, which correlated with BMI z-score. Interestingly, miR-146a-5p was also correlated with HOMA-IR index. While only miR-18a-5p was upregulated in the OW/OB children, independently of their degree of insulin sensitivity, miR-146-5p, miR-423-3p and miR-152-3p were associated with insulin resistance. SIGNIFICANCE: The present study provides evidence of molecular alterations that occur early in life in prepubertal obesity. These alterations may potentially be crucial for targeted prevention or prompt precision therapeutic development and subsequent interventions.
Subject(s)
Circulating MicroRNA , Insulin Resistance , MicroRNAs , Pediatric Obesity , Humans , Child , Insulin Resistance/genetics , Circulating MicroRNA/genetics , Pediatric Obesity/genetics , Pediatric Obesity/epidemiology , Insulin , MicroRNAs/genetics , Body Mass IndexABSTRACT
OBJECTIVE: The objective of this study was to quantify the effects of a 4-week, supervised, high-intensity interval training (HIIT) on intrahepatic triglyceride content (IHTG, percentage), cardiorespiratory fitness (CRF), and cardiometabolic markers in adolescents with obesity. METHODS: A total of 40 adolescents (age 13-18 y, BMI 36.7 ± 5.8 kg/m2 ) at risk for metabolic dysfunction-associated steatotic liver disease (MASLD) based on obesity and elevated Fibroscan measured controlled attenuation parameter (CAP) scores were randomized to HIIT three times a week for 4 weeks (n = 34) or observation (control; n = 6). Liver magnetic resonance imaging proton-density fat-fraction (MRI-PDFF), CAP, oral glucose tolerance test, serum alanine aminotransferase, dual-energy x-ray absorptiometry, and CRF tests were performed before and after intervention. Within- and between-group differences were compared. RESULTS: A total of 13 (38%) and 4 (66%) children had MASLD by MRI-PDFF (IHTG ≥ 5%) in the HIIT and control groups, respectively. The implemented HIIT protocol had no impact on CRF or IHTG (baseline 5.26%, Δ = -0.31 percentage points, 95% CI: -0.77 to 0.15; p = 0.179), but it decreased the 2-h glucose concentration (baseline 116 mg/dL, Δ = -11 mg/dL; 95% CI: -17.6 to -5.5; p < 0.001). When limiting the analysis to participants with MASLD (n = 17), HIIT decreased IHTG (baseline 8.81%, Δ = -1.05 percentage points, 95% CI: -2.08 to -0.01; p = 0.048). Between-group comparisons were not different. CONCLUSIONS: The implemented exercise protocol did not reduce IHTG, but it led to modest improvement in markers of cardiometabolic health.
Subject(s)
Cardiovascular Diseases , Metabolic Diseases , Pediatric Obesity , Adolescent , Humans , Exercise , Liver/diagnostic imaging , Overweight , Pediatric Obesity/diagnostic imaging , Pediatric Obesity/therapyABSTRACT
Non-alcoholic fatty liver disease (NAFLD), is one of the main liver diseases in the US and the world which often is related to obesity. Previously, we reported short- and long-term consumption of soy protein isolate diet with high isoflavones can reduce liver steatosis in the male and female obese Zucker rat model. However, the effects of high vs. low soy isoflavones on NAFLD is less known. The objectives of the present study were to examine the role of isoflavones levels in soy protein concentrate diets on protection against NAFLD in an obese rat model. Forty-two 6-week old lean (L, n = 21) and obese (O, n = 21) Zucker rats were randomly assigned to 1 of 3 dietary groups: casein diet (C = control), soy protein concentrate with low isoflavones (LIF), or soy protein concentrate with high isoflavones (HIF) for 9 weeks. Rats were weighed twice weekly. After 9 weeks, rats were sacrificed and samples of livers were taken for histopathological analysis. Serums were collected to measure ALT and AST levels. Results indicate that obese rats gained significantly more weight than lean rats for all three diet groups (P < 0.001). No significant difference in body weight between LC, LLIF and LHIF was noted. However, the OLIF and OHIF rats gained significantly more weight than OC rats (P < 0.001). Liver steatosis scores were significantly greater in obese rats compared to lean rats (P < 0.001). The OLIF and OHIF-fed rats had significantly reduced steatosis scores than OC rats (P = 0.013 and P < 0.001, respectively). The serum ALT levels were significantly greater in OC, OLIF and OHIF compared to LC, LLIF and LHIF, respectively (P < 0.001, P < 0.001, and P = 0.011). AST serum levels were greater in OC and OLIF compared to LC and LLIF, respectively (P = 0.001 and P = 0.022). In summary, we found that soy protein concentrate with isoflavones protects against liver steatosis and the protection is greater with a higher concentration of isoflavones.
ABSTRACT
Gestational diabetes mellitus (GDM) poses a significant health concern for both mother and offspring. Exercise has emerged as a cornerstone of glycemic management in GDM. However, most research regarding this topic examines aerobic training (AT), despite substantial evidence for the effectiveness of resistance training (RT) in improving dysregulated glucose in other groups of people with diabetes, such as in type 2 diabetes mellitus (T2DM). Thus, the purpose of this paper is to review research that examined the impact of RT on markers of glucose management in GDM, and to discuss future research directions to determine the benefits of RT in GDM. Based on the current evidence, RT is effective in reducing insulin requirement, especially in overweight women, reducing fasting glucose concentrations, and improving short-term postprandial glycemic control. However, the number of studies and findings limit conclusions about the impact of RT on risk of GDM, fasting insulin concentrations, insulin resistance, ß-cell function, and intra-exercise glucose management. Overall, current evidence is accumulating to suggest that RT is a promising non-pharmacological tool to regulate circulating glucose concentrations in women with GDM, and a potential alternative or supplement to AT.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetes, Gestational , Resistance Training , Pregnancy , Female , Humans , Diabetes, Gestational/therapy , Insulin , Glucose , Blood GlucoseABSTRACT
The purpose of this study was to determine the effect of exercise during pregnancy in sedentary women with obesity on longitudinal changes in long-chain acylcarnitine (LC-AC) concentrations. We hypothesized that exercise training would significantly decrease circulating LC-ACs throughout gestation compared with a nonexercise control group. Pregnant women with obesity considered otherwise healthy [n = 80, means ± SD; body mass index (BMI): 36.9 ± 5.7 kg/m2] were randomized into an exercise (n = 40, aerobic/resistance 3 times/wk, â¼13th gestation week until birth) or a nonexercise control (n = 40) group. At gestation week 12.2 ± 0.5 and 36.0 ± 0.4, a submaximal exercise test was conducted, and indirect calorimetry was used to measure relative resting energy expenditure (REE), as well as respiratory exchange ratio (RER) at rest. Fasting blood samples were collected and analyzed for LC-AC concentrations. Fitness improved with prenatal exercise training; however, exercise training did not affect circulating LC-AC. When groups were collapsed, LC-ACs decreased during gestation (combined groups, P < 0.001), whereas REE (kcal/kg/day, P = 0.008) increased. However, average REE relative to fat-free mass (FFM) (kcal/kg FFM/day) and RER did not change. There was an inverse relationship between the change in RER and all LC-ACs (except C18:2) throughout gestation (C14: r = -0.26, P = 0.04; C16: r = -0.27, P = 0.03; C18:1: r = -0.28, P = 0.02). In summary, a moderate-intensity exercise intervention during pregnancy in women with obesity did not alter LC-ACs concentrations versus control, indicating that the balance between long-chain fatty acid availability and oxidation neither improved nor worsened with an exercise intervention.NEW & NOTEWORTHY This research showed that a moderate-intensity prenatal exercise program, consisting of aerobic and resistance training, did not negatively impact normal alterations in substrate supply and demand for the mother and the offspring throughout gestation. Findings provide support for metabolic safety of exercise during pregnancy.