No 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.

Objectives Human milk (HM) fatty acid content is, influenced by both maternal adiposity and diet. The objective of this study was to determine the impact of a Mediterranean meal plan on HM fatty acid content in women with obesity. Methods In this pilot study, thirteen women with obesity (body mass index (BMI) ≥ 30 kg/m2) enrolled at five months post-partum and were provided a Mediterranean meal plan for four weeks. Nutrition Data System for Research was used to assess participants’ diet during the study. HM was collected at baseline and after the 4-week intervention. Cytokines were measured using multi-spot assays and the fatty acid composition of triglycerides determined using a UHPLC electrospray ionization mass spectrometry. Triglycerides containing a particular fatty acid species were normalized to the total abundance of all triglyceride species detected in each sample. Wilcoxon signed-rank tests were used to assess changes in participant diet and HM composition, and repeated measures correlations were used to test associations of paired measures. Summary statistics are presented as mean ± standard deviation. Results During the intervention, the ratio of the maternal intake of ω6 and ω3 fatty acids (ω6: ω3) significantly decreased (8.86 ± 1.60 vs. 4.63 ± 1.25, P &lt; 0.001) and was positively correlated with HM levels of leptin and tumor necrosis factor-α (r = 0.64, p = 0.024 and r = 0.67, p = 0.017, respectively). Levels of human milk 20:3 (0.588 ± 0.085% vs. 0.483 ± 0.080%, P &lt; 0.001) and 22:4 (0.057 ± 0.012% vs. 0.050 ± 0.011%, p = 0.01) fatty acids were significantly decreased following the intervention. Maternal intake of ω6: ω3 positively correlated with HM 20:3 and 22:4 fatty acid concentrations (r = 0.78, p = 0.001 and r = 0.71, p = 0.005, respectively). Conclusions A 4-week Mediterranean meal plan modulated the fatty acid content in HM from women with obesity. There was an association between maternal ω6: ω3 intake and HM fatty acid content, supporting a role for maternal diet in modulating HM composition. Future studies are needed to investigate the effect of the intervention on specific fatty acids and whether the observed changes in HM impact infant growth or development. Funding Sources USDA ARS #6026–51,000-010–05S and #6026–51,000-012–06S, NIH/NIDDK R01DK107516, Arkansas Children's Research Institute/Arkansas Biosciences Institute GR037121.

No abstract