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Proteomic pattern of breast milk discriminates obese mothers with infants of delayed weight gain from normal-weight mothers with infants of normal weight gain.

ABSTRACT: We previously reported that exclusively breastfed infants born to mothers with pregestational obesity gain less weight during the first month after birth than those born to mothers of normal pregestational weight. This issue is potentially important since lower weight gain in breastfed infants of obese mothers might increase the risk of developing later obesity. Breast milk quality and quantity, together with breastfeeding practice, possibly influence infants' feeding behavior, appetite control, and regulation of growth later in life. The issue of whether breast milk protein patterns from obese mothers differ in composition from those of non-obese mothers remains largely unexplored. Here, we established a breast milk proteomic pattern that discriminates obese mothers and infants with delayed weight gain at 1 month after birth from normal-weight mothers with infants of the same age and with normal weight gain. Obese mothers were matched to normal-weight mothers (n = 26; body mass index 33.5 ± 3.2 vs 21.5 ± 1.5 kg·m-2). The mean weight gain of infants in the obese group at 1 month after birth was 430.8 g lower than that of the infants in the control group. Analysis of the breast milk delipidized fraction by surface-enhanced laser desorption/ionization on CM10 and Q10 arrays was followed by MS-assisted purification and LC-MS/MS microsequencing of a selected biomarker. We identified 15 candidate protein biomarkers, seven of which were overexpressed in the obese group and eight in the normal-weight group. One of the most significant candidate biomarkers, overexpressed in the obese group, was identified as a fragment of the sixth extracellular domain of the polymeric immunoglobulin receptor. Further structural identification of these candidate biomarkers and their validation in clinical assays may facilitate the development of a predictive immunoassay.

SUBMITTER: Atanassov C

PROVIDER: S-EPMC6443869 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Proteomic pattern of breast milk discriminates obese mothers with infants of delayed weight gain from normal-weight mothers with infants of normal weight gain.

Atanassov Christo C Viallemonteil Etienne E Lucas Charlotte C Perivier Marylise M Claverol Stéphane S Raimond Roland R Hankard Régis R

FEBS open bio 20190315 4

We previously reported that exclusively breastfed infants born to mothers with pregestational obesity gain less weight during the first month after birth than those born to mothers of normal pregestational weight. This issue is potentially important since lower weight gain in breastfed infants of obese mothers might increase the risk of developing later obesity. Breast milk quality and quantity, together with breastfeeding practice, possibly influence infants' feeding behavior, appetite control, ...[more]

PMID: 30984547

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Project description:BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as "metabolically normal obese" (MNO), but not those defined as "metabolically abnormal obese" (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain-induced metabolic dysfunction. TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170. FUNDING. This work was supported by NIH grants UL1 RR024992 (Clinical Translational Science Award), DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Center Grant), and UL1 TR000450 (KL2 Award); a Central Society for Clinical and Translational Research Early Career Development Award; and by grants from the Longer Life Foundation and the Kilo Foundation.

Project description:BACKGROUND:Mothers In Motion (MIM), a community-based lifestyle behavioral intervention, was designed and conducted to help low-income overweight and obese young mothers prevent further weight gain via promotion of stress management, healthy eating, and physical activity. This paper presents intervention effect on body weight (primary outcome) and summarizes lessons learned. METHODS:Participants (N?=?612) were recruited from 7 Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) offices in Michigan and were individually randomized to an intervention n=?410) or a comparison (n?=202) group (2: 1 ratio). During the 16-week intervention, intervention participants watched theory-based culturally sensitive videos (in DVD format) featuring peers from the target audience to learn skills for managing stress, eating healthier, and being more physically active. They also dialed into peer support group teleconferences to enhance skills learned in the videos and increase motivation for lifestyle behavioral changes. Body weight, the primary outcome, was measured at baseline, immediately after the 16-week intervention, and 3 months after the 16-week intervention. Intervention effect was tested via general linear mixed model for repeated measures, using baseline measures as adjusting covariates. RESULTS:At baseline, the mean age of the participants was 28.5?±?5.0 years (intervention: 28.4?±?5.0, comparison: 28.9?±?5.0); the mean body weight was 190.2?±?1.4 lbs (intervention: 191.8?±?30.0, comparison: 188.5?±?29.1); and the mean body mass index (BMI) was 32.2?±?4.4 (intervention: 32.2?±?4.4, comparison: 31.7?±?4.2). Of sample, 64.7% were obese. At 3 months after the 16-week intervention, no significant weight differences were found between the intervention (188.3?±?10.6 lbs, BMI: 31.6?±?1.8) and comparison groups (187.7?±?10.6 lbs, BMI: 31.53?±?1.8) when controlling for baseline body weight. CONCLUSIONS:This lifestyle behavioral intervention that focused on stress management, healthy eating and physical activity was not effective in helping low-income overweight and obese young mothers prevent further weight gain. TRIAL REGISTRATION:Clinical Trials NCT01839708 . This trial was registered retrospectively on February 28, 2013.

Project description:Over 45% of American women 20-39 years old are at risk for type 2 diabetes, cardiovascular disease, and other health conditions because they are overweight or obese. The prevalence of overweight and obesity is disproportionately high among low-income women. This paper describes the study design and rationale of a community based intervention (Mothers In Motion, MIM) aimed to prevent weight gain among low-income overweight and obese mothers 18-39 years old by promoting stress management, healthy eating, and physical activity.Peer recruiters approach participants from 5 Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in Michigan. The MIM delivers theory-based, culturally-sensitive intervention messages via a combination of DVDs and peer support group teleconferences (PSGTs). The DVD features African American and white overweight and obese WIC mothers who participated in a healthy lifestyle intervention patterned after MIM. The PSGTs are led by paraprofessionals from Michigan State University Extension and WIC providers in Michigan who are trained in motivational interviewing and group facilitation skills. Participants are randomly assigned to an intervention (n=350) or comparison group (n=175). The intervention group receives a 16-week intervention on a weekly or bi-weekly basis. Participants are asked to watch 10 MIM DVD chapters at home and join 10 PSGT sessions by phone. The comparison group receives printed educational materials. The primary outcome is body weight. Secondary outcomes include dietary fat, fruit, and vegetable intake; physical activity; stress, and affect. Mediators are self-efficacy, emotional coping response, social support, and autonomous motivation. Telephone interviews and in-person data collection at WIC offices occur at 3 time points: baseline, immediately, and 3 months after the 16-week intervention.If MIM shows effectiveness, it could have a favorable impact on public health and community programs. The DVDs and PSGTs will be disseminated in WIC, Extension, clinical practice that promote healthy lifestyles for similar target audiences to make a broad contribution to the prevention of weight gain in low-income mothers. Also, our methodology can be adapted by researchers and community stakeholders to help other low-income populations prevent weight gain.Clinical Trials Number: NCT01839708.

Project description:BackgroundBreast milk has abundant extracellular vesicles (EVs) containing various biological molecules (cargo), including miRNAs. EVs are not degraded in the gastrointestinal system and circulation; thus, breast milk EVs (bEVs) are expected to interact with other organs in breastfed infants and modify the gene expression of recipient cells using miRNAs. Maternal pre-pregnancy BMI is a critical factor influencing the composition of breast milk. Thus, in mothers with obesity, miRNAs in bEVs can be altered, which might be associated with adverse health outcomes in infants. In this study, we examined 798 miRNAs to determine which miRNAs are altered in the bEVs of mothers with obesity and their potential impact on breastfed infants.MethodsWe recruited healthy nursing mothers who were either of normal weight (BMI < 25) or with obesity (BMI ≥ 30) based on their pre-pregnancy BMI, and delivered a singleton baby in the prior 6 months. EVs were isolated from breast milk with ultracentrifugation. bEV characteristics were examined by flow cytometry and fluorescence imaging of EV markers. A total of 798 miRNAs were screened using a NanoString human miRNA panel to find differentially expressed miRNAs in bEVs of mothers with obesity compared to mothers of normal weight.ResultsWe included 65 nursing mothers: 47 of normal weight and 18 with obesity based on pre-pregnancy BMI. After bEV isolation, we confirmed the expression of various EV markers. Out of 37 EV markers, CD326 (EpCaM) was the most highly expressed in bEVs. The most abundant miRNAs in bEVs include miR-30b-5p, miR-4454, miR-494-3p, and let-7 miRNAs. Target genes of the top 10 miRNAs were associated with cancer, prolactin pathway, EGFR, ErbB, and FoxO signaling pathway. In bEVs of mothers with obesity, 19 miRNAs were differentially expressed (adjusted p < 0.05 cut-off), which include miR-575, miR-630, miR-642a-3p, and miR-652-5p. These miRNAs and their target genes were associated with neurological diseases and psychological disorders.ConclusionIn this study, we characterized bEVs and demonstrated altered miRNAs in bEVs of mothers with obesity and identified the pathways of their potential target genes. Our findings will provide insight for future studies investigating the role of bEVs in breastfed infants.

Project description:BackgroundRecruitment and retention are key functions for programs promoting nutrition and other lifestyle behavioral changes in low-income populations. This paper describes strategies for recruitment and retention and presents predictors of early (two-month post intervention) and late (eight-month post intervention) dropout (non retention) and overall retention among young, low-income overweight and obese mothers participating in a community-based randomized pilot trial called Mothers In Motion.MethodsLow-income overweight and obese African American and white mothers ages 18 to 34 were recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children in southern Michigan. Participants (n = 129) were randomly assigned to an intervention (n = 64) or control (n = 65) group according to a stratification procedure to equalize representation in two racial groups (African American and white) and three body mass index categories (25.0-29.9 kg/m(2), 30.0-34.9 kg/m(2), and 35.0-39.9 kg/m(2)). The 10-week theory-based culturally sensitive intervention focused on healthy eating, physical activity, and stress management messages that were delivered via an interactive DVD and reinforced by five peer-support group teleconferences. Forward stepwise multiple logistic regression was performed to examine whether dietary fat, fruit and vegetable intake behaviors, physical activity, perceived stress, positive and negative affect, depression, and race predicted dropout as data were collected two-month and eight-month after the active intervention phase.ResultsTrained personnel were successful in recruiting subjects. Increased level of depression was a predictor of early dropout (odds ratio = 1.04; 95% CI = 1.00, 1.08; p = 0.03). Greater stress predicted late dropout (odds ratio = 0.20; 95% CI = 0.00, 0.37; p = 0.01). Dietary fat, fruit, and vegetable intake behaviors, physical activity, positive and negative affect, and race were not associated with either early or late dropout. Less negative affect was a marginal predictor of participant retention (odds ratio = 0.57; 95% CI = 0.31, 1.03; p = 0.06).ConclusionDropout rates in this study were higher for participants who reported higher levels of depression and stress.Trial registrationCurrent Controlled Trials NCT00944060.

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Dataset Information

Proteomic pattern of breast milk discriminates obese mothers with infants of delayed weight gain from normal-weight mothers with infants of normal weight gain.

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Proteomic pattern of breast milk discriminates obese mothers with infants of delayed weight gain from normal-weight mothers with infants of normal weight gain.

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