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Effects of short-term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial.
Tas, E, Landes, RD, Diaz, EC, Bai, S, Ou, X, Buchmann, R, Na, X, Muzumdar, R, Børsheim, E, Dranoff, JA
Obesity (Silver Spring, Md.). 2023;(11):2740-2749
Abstract
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.
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Circulating microRNA levels differ in the early stages of insulin resistance in prepubertal children with obesity.
Santos, D, Porter-Gill, P, Goode, G, Delhey, L, Sørensen, AE, Rose, S, Børsheim, E, Dalgaard, LT, Carvalho, E
Life sciences. 2023;:121246
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Abstract
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.
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Circulating long-chain acylcarnitine concentrations are not affected by exercise training in pregnant women with obesity.
Allman, BR, Spray, BJ, Lan, RS, Andres, A, Børsheim, E
Journal of applied physiology (Bethesda, Md. : 1985). 2022;(2):470-476
Abstract
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, ∼13th 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.
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Breastfeeding duration modifies the association between maternal weight status and offspring dietary palmitate oxidation.
Diaz, EC, Williams, DK, Cotter, M, Sims, CR, Wolfe, RR, Andres, A, Børsheim, E
The American journal of clinical nutrition. 2022;(2):404-414
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BACKGROUND Offspring of obese rodents develop a metabolic phenotype that favors fat deposition. Data regarding the impact of maternal obesity programing of offspring fuel usage in humans is scarce. OBJECTIVE The objective of this study was to explore the association between maternal weight status and dietary palmitate oxidation (DPO) in 2-y-old offspring, taking into consideration potential confounders and modifiers. METHODS Women (n = 56) were enrolled by the first trimester of gestation. Maternal physical activity (PA; measured with accelerometers) at enrollment and gestational weight gain (GWG) were measured. Offspring sex, race, and breastfeeding (BF) duration were self-reported. Human milk (HM) composition was determined at 6 mo postpartum. At age 2 y, dietary quality [healthy eating index (HEI)] and parental feeding practices [Child Feeding Questionnaire (CFQ)] were assessed. DPO in 2-y-olds (2-yo-DPO) was measured using deuterated palmitic acid. Generalized linear regression analysis was used to model the associations of 2-yo-DPO with maternal weight status [normal weight (NW), BMI <25 (in kg/m2) compared with excessive weight (EW), BMI ≥25]. RESULTS DPO was higher in offspring of women with EW compared with NW (2.1 ± 1.2%/h compared with 1.4 ± 0.7%/h, P = 0.03). Maternal weight status interacted with BF duration in association with 2-yo-DPO (log ß: 0.05, P = 0.04). Specifically, 2-yo-DPO was higher in the EW compared with NW group if BF duration was ≥9 mo. HM insulin (log ß: 0.35, P = 0.002) and HM leptin (log ß: 0.81, P = 0.001) concentrations directly associated with 2-yo-DPO. PA (log ß: 0.06, P = 0.013), parental feeding restriction (log ß: 0.05, P < 0.0001), and male sex (log ß: 0.54, P < 0.001) were positively associated with 2-yo-DPO. HEI was negatively associated with 2-yo-DPO (log ß:-0.03, P < 0.0001). CONCLUSIONS Higher 2-yo-DPO in offspring of women with EW compared with NW were driven by BF duration. Higher HM insulin and leptin concentrations in women with EW may explain these finding. More studies are needed to confirm these results. This trial was registered at clinicaltrials.gov as NCT03281850.
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Digital Intervention Strategies for Increasing Physical Activity Among Preschoolers: Systematic Review.
Swindle, T, Poosala, AB, Zeng, N, Børsheim, E, Andres, A, Bellows, LL
Journal of medical Internet research. 2022;24(1):e28230
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Digital strategies to improve the diet and activity of pre-schoolers are increasing due to their accessibility and relatively low cost to set up. This systematic review of 8 studies aimed to determine the quality of the studies that have been performed to date, and to determine the effectiveness of the digital strategies used to increase physical activity. The results showed that the studies reviewed had a small sample size. Only 2 studies showed positive changes in physical activity of pre-schoolers and these approaches were child led, but the studies were low quality. Parent focused interventions did not improve the physical activity of pre-schoolers. It was concluded that digital child-centred activities may be of benefit to physical activity in pre-schoolers, however parent-focused digital interventions may be ineffective. This study could be used by healthcare professionals to understand the importance of using digital strategies which engage children to improve their health.
Abstract
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.
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Effect of excess weight and insulin resistance on DNA methylation in prepubertal children.
Barbosa, P, Landes, RD, Graw, S, Byrum, SD, Bennuri, S, Delhey, L, Randolph, C, MacLeod, S, Reis, A, Børsheim, E, et al
Scientific reports. 2022;(1):8430
Abstract
Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play a role in the development of insulin resistance. This study evaluates how the BMI z-score (BMIz) and the homeostatic model assessment of insulin resistance (HOMA-IR), alone or in combination, relate to clinical outcomes and DNA methylation patterns in prepubertal children. DNA methylation in peripheral blood mononuclear cells (PBMCs) and clinical outcomes were measured in a cohort of 41 prepubertal children. Children with higher HOMA-IR had higher blood pressure and plasma lactate levels while children with higher BMIz had higher triglycerides levels. Moreover, the DNA methylation analysis demonstrated that a 1 unit increase in the BMIz was associated with a 0.41 (95% CI: 0.29, 0.53) increase in methylation of a CpG near the PPP6R2 gene. This gene is important in the regulation of NF-kB expression. However, there was no strong evidence that the BMIz and the HOMA-IR were synergistically related to any clinical or DNA methylation outcomes. In summary, the results suggest that obesity and insulin resistance may impact metabolic health both independently in prepubertal children. In addition, obesity also has an impact on the DNA methylation of the PPP6R2 gene. This may be a novel underlying starting point for the systemic inflammation associated with obesity and insulin resistance, in this population.
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Resistance Training as a Countermeasure in Women with Gestational Diabetes Mellitus: A Review of Current Literature and Future Directions.
Allman, BR, McDonald, S, May, L, Børsheim, E
Sports medicine (Auckland, N.Z.). 2022;(12):2871-2888
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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, β-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.
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Effect of a dietary and exercise intervention in women with overweight and obesity undergoing fertility treatments: protocol for a randomized controlled trial.
Fawcett, K, Martinez, A, Crimmins, M, Sims, C, Børsheim, E, Andres, A
BMC nutrition. 2021;(1):51
Abstract
BACKGROUND Distinct molecular, inflammatory, and metabolic signatures are present in oocytes and follicular fluid derived from women with obesity when compared to those derived from normal weight women, which suggest existing signals that may program future offspring for metabolic diseases. This study aims to assess the feasibility and efficacy of a peri-conception nutrition and exercise intervention on mitigating obesity-associated changes in oocyte gene expression profiles and follicular fluid metabolites. METHODS This single blinded randomized control trial will include 120 women with a BMI of 25-45 kg/m2, ≥21 years of age, and undergoing in vitro fertilization (IVF) treatments. Participants will be randomized to standard of care (N = 60) or an intervention group (N = 60) in a block design by polycystic ovary syndrome status. The intervention will combine a dietary component (Mediterranean meal plan) with exercise prescription following the Physical Activity Guidelines for Americans. Participants will be assessed pre- and post-intervention. The standard of care group will be offered to join the intervention group if the IVF treatments are unsuccessful as a cross over design. Recruitment is anticipated to start in July of 2021. Primary outcomes will include single oocyte gene expression profiles and follicular fluid metabolites. Mann-Whitney U nonparametric tests will be used to assess potential differences for each stratum. Follicular fluid and serum metabolites will be analyzed using a one-factor Analysis of Covariance (ANCOVA) at four levels, pair-wise comparisons using Tukey-Kramer post-hoc tests will be used to identify groups whose means differ significantly while retaining the family-wise error rate at 5%. When the design is balanced, two-way Analysis of Variance (ANOVA), or non-parametric Friedman test will be used in data analysis. Additionally, general linear models and ANCOVA may be used to control for covariates. Significance will be set at p < 0.05. Findings will be disseminated via peer-reviewed manuscripts and presentations at scientific conferences. DISCUSSION This study will provide novel data and key information on the impact of a dietary and exercise intervention on oocyte gene expression and follicular fluid content. Results will demonstrate the potential of such intervention in mitigating obesity-induced changes in oocyte gene expression and follicular fluid metabolites. TRIAL REGISTRATION ClinicalTrials.gov ( NCT04273048 ): submitted November 13, 2019; posted February 17, 2020.
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Markers of branched-chain amino acid catabolism are not affected by exercise training in pregnant women with obesity.
Allman, BR, Spray, BJ, Mercer, KE, Andres, A, Børsheim, E
Journal of applied physiology (Bethesda, Md. : 1985). 2021;(3):651-659
Abstract
Despite the role of branched-chain amino acids (BCAAs) in physiological processes such as nutrient signaling and protein synthesis, there is ongoing debate about the link between circulating BCAAs and insulin resistance (IR) in various populations. In healthy women, IR mildly increases during pregnancy, whereas both BCAAs and markers of BCAA catabolism decrease, indicating that fetal growth is being prioritized. Exercise reduces IR in nonpregnant adults, but less is known about the effect of exercise during pregnancy in women with obesity on IR and BCAA breakdown. The aim of this study was to determine the effect of a moderate-intensity exercise intervention during pregnancy on maternal circulating BCAAs and markers of BCAA catabolism [short-chain acylcarnitines (ACs)], and their associations with IR. Healthy obese [n = 80, means ± SD; body mass index (BMI): 36.9 ± 5.7 kg/m2] pregnant women were randomized into an exercise (n = 40, aerobic/resistance 3×/wk, ∼13th gestation week until birth) or a nonexercise control (n = 40) group. Blood was collected at 12.2 ± 0.5 and 36.0 ± 0.4 gestation weeks and analyzed for BCAA-derived acylcarnitine concentrations as markers of BCAA breakdown toward oxidative pathways, and glucose and insulin concentrations [updated homeostatic model assessment of IR (HOMA2-IR)]. After adjusting for HOMA2-IR, there were no interaction effects of group by time. In addition, there was a main positive effect of time on HOMA2-IR (12 wk: 2.3 ± 0.2, 36 wk: 3.0 ± 0.2, P = 0.003). A moderate-intensity exercise intervention during pregnancy in women with obesity was not associated with changes in BCAA-derived ACs versus standard of care. The decrease in BCAA-derived ACs throughout gestation could not be explained by IR.NEW & NOTEWORTHY This research showed an increase in insulin resistance (IR) and decrease in branched-chain amino acid catabolism throughout gestation in women with obesity, and addition of a moderate exercise intervention (known to attenuate IR in nonpregnant populations) did not alter these shifts. Findings provide support for metabolic safety of exercise during pregnancy.
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Dietary Protein Requirements in Children: Methods for Consideration.
Hudson, JL, Baum, JI, Diaz, EC, Børsheim, E
Nutrients. 2021;(5)
Abstract
The current protein requirement estimates in children were largely determined from studies using the nitrogen balance technique, which has been criticized for potentially underestimating protein needs. Indeed, recent advances in stable isotope techniques suggests protein requirement as much as 60% higher than current recommendations. Furthermore, there is not a separate recommendation for children who engage in higher levels of physical activity. The current evidence suggests that physical activity increases protein requirements to support accretion of lean body masses from adaptations to exercise. The indicator amino acid oxidation and the 15N-end product methods represent alternatives to the nitrogen balance technique for estimating protein requirements. Several newer methods, such as the virtual biopsy approach and 2H3-creatine dilution method could also be deployed to inform about pediatric protein requirements, although their validity and reproducibility is still under investigation. Based on the current evidence, the Dietary Reference Intakes for protein indicate that children 4-13 years and 14-18 years require 0.95 and 0.85 g·kg-1·day-1, respectively, based on the classic nitrogen balance technique. There are not enough published data to overturn these estimates; however, this is a much-needed area of research.