Contexte. La corpulence de la mère au moment de la conception et son évolution pondérale pendant la grossesse ont été mises en relation dans de nombreuses études avec le poids de naissance de l’enfant et sa croissance postnatale, ainsi qu’avec le risque ultérieur d’obésité et d’anomalies métaboliques de la mère et de l’enfant. Néanmoins, peu d’études se sont intéressées à la trajectoire pondérale de la mère avant grossesse et à son lien avec le déroulement de la grossesse et avec la croissance et l’adiposité des enfants.Objectif : Etudier les relations entre différents paramètres de l’histoire pondérale de la mère avant et pendant la grossesse et leurs liens avec le risque de diabète gestationnel et la corpulence des enfants.Populations. Nous avons utilisé les données de deux cohortes mère-enfant françaises : ELFE et EDEN. L’étude Elfe (Etude longitudinale française depuis l’enfance) a inclus 18329 nouveau-nés dans un échantillon aléatoire de 344 maternités en 2011 en France métropolitaine. La cohorte EDEN (l’Étude des Déterminants pré- et postnatals du développement et de la santé de l’Enfant) a recruté 2002 femmes enceintes dans les maternités de Nancy et Poitiers entre 2003 et 2006. Dans les deux cohortes nous avons utilisé des données du dossier obstétrical et des questionnaires remplis par les parents. Dans la cohorte EDEN nous disposions également des données des examens cliniques des femmes pendant la grossesse et en post-partum, du nouveau-né et de l’enfant à 5-6 ans, incluant l’estimation de la composition corporelle par impédancemétrie des enfants à 5-6 ans.Résultats. Dans la cohorte Elfe, un régime avant grossesse, une perte ou un gain de poids important avant grossesse étaient associés à un gain de poids pendant la grossesse plus important, indépendamment de l’IMC pré-conceptionnel et du statut socio-économique. L’association positive entre la perte pondérale avant grossesse et la prise de poids gestationnelle était plus marquée chez les femmes obèses en début de grossesse ou ayant suivi un régime avant la grossesse. Les femmes ayant pris beaucoup de poids dans l’année avant grossesse présentaient un risque plus élevé de diabète gestationnel, indépendamment de la corpulence atteinte à la conception.Dans la cohorte EDEN, l’IMC maternel pré-conceptionnel était positivement associé à l’IMC, au pourcentage de masse grasse et à une distribution plus défavorable de l’adiposité (tronculaire, viscérale) des enfants à 5-6 ans. Ces associations étaient observées indépendamment de la prise de poids pendant la grossesse et du statut socio-économique des femmes. Une analyse fine de la forme des relations a permis de souligner l’existence de liens essentiellement aux deux extrémités de la corpulence maternelle. Après ajustement sur l’IMC pré-conceptionnel, le gain pondéral gestationnel était positivement associé au Z-score d’IMC des enfants à 5-6 ans, surtout chez les femmes maigres avant grossesse. Un ajustement supplémentaire sur le poids de naissance des enfants a diminué la force des associations entre le Z-score d’IMC des enfants et l’IMC maternel ou la prise de poids pendant la grossesse, mais les deux associations restaient significatives.Conclusion. Une perte de poids avant grossesse, surtout si elle est intentionnelle, semble engendrer une augmentation compensatoire du gain de poids pendant la grossesse. La prise de poids importante avant grossesse, au-delà de la corpulence maternelle en début de grossesse, pourrait être considérée comme un facteur de risque indépendant de diabète gestationnel. A l’âge de 5-6 ans, l’effet rémanent de l’environnement nutritionnel intra-utérin sur l’adiposité des enfants n’est détecté que chez les femmes maigres ou très obèses avant grossesse. D’autres études chez l’enfant sont nécessaires pour pouvoir conclure sur des recommandations de perte de poids avant grossesse chez les femmes en surpoids et obèses. / Context. Maternal BMI at conception and weight gain during pregnancy were related in numerous studies with offspring’s birth weight and postnatal growth, as well as with mothers’ and children’s obesity and metabolic risk later on. Nevertheless, few studies addressed the weight trajectory of the mother before pregnancy and its association with children’s growth and adiposity.Objective: To study the associations between different parameters of maternal weight history before and during pregnancy and their relations with the risk of gestational diabetes and with children’s BMI and adiposity.Populations. We used data from two French mother-child cohorts: ELFE and EDEN. The ELFE study (Etude longitudinale française depuis l’enfance) included 18329 newborns in a random sample of 344 maternity wards in 2011 in mainland France. The EDEN cohort (study of pre- and early postnatal determinants of child development and health) recruited 2002 pregnant women in the maternity wards of Nancy and Poitiers between 2003 and 2006. We used data from obstetric files and from questionnaires filled-in by parents in both cohorts. In addition, the EDEN cohort had data from clinical examinations (of mothers during pregnancy and after delivery and of children at birth and at 5-6 years of age), including the estimation of children’s body composition by bio-impedancemetry at 5-6 years.Results. In the ELFE study, either maternal dieting to lose weight or an important weight gain or loss in the year before pregnancy were associated with a higher weight gain during pregnancy, independently of maternal pre-pregnancy BMI and socioeconomic status. The positive association between weight loss before pregnancy and weight gain during pregnancy was stronger in women who were obese or who had reported weight-reducing diets before pregnancy. Women who had gained an important amount of weight in the year before pregnancy had a higher risk of gestational diabetes, independently of the BMI reached at the beginning of pregnancy.Our analyses on the EDEN cohort showed that maternal pre-pregnancy BMI was positively related with children’s BMI, fat mass percent and central adiposity at 5-6 years of age. These associations were observed independently of women’s weight gain during pregnancy and socioeconomic status. A more thorough analysis of the shape of these relations showed associations essentially at the extremities of the maternal BMI range. Gestational weight gain was positively associated with children’s BMI Z-score at 5-6 years, after adjustment for maternal pre-pregnancy BMI, especially in women who were thin before pregnancy. Additional adjustment for children’s birth weight decreased the force of associations between children’s BMI Z-score and both maternal pre-pregnancy BMI and gestational weight gain, but both associations remained statistically significant.Conclusion. Important weight loss before pregnancy, especially if intentional, seems to enhance a compensatory increase in gestational weight gain. Important weight gain before pregnancy, beyond its role in maternal BMI reached before pregnancy, might be considered as an independent risk factor of gestational diabetes. At 5-6 years, the persistent effect of the intra-uterine environment on children’s BMI and adiposity is only detected in women who were thin or severely obese before pregnancy. Additional studies on children are necessary in order to conclude on weight loss recommendations before pregnancy in overweight and obese women.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18646号 / 医博第3945号 / 新制||医||1006(附属図書館) / 31560 / 京都大学大学院医学研究科医学専攻 / (主査)教授 川上 浩司, 教授 横出 正之, 教授 千葉 勉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied. Here, we tested the hypothesis that extensive weight loss in response to bariatric surgery (BS) causes AT gene expression changes, which may affect energy and lipid metabolism, inflammation and secretory function of AT. We assessed gene expression changes by whole genome expression chips in AT samples obtained from six morbidly obese individuals, who underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en-Y gastric bypass as second step surgery after 12 ± 2 months. Global gene expression differences in VAT and subcutaneous (S)AT were analyzed through the use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered gene expressions were PCR-validated in 16 individuals, which also underwent a two-step surgery intervention. We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss. We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss.

Background: Liver fibrosis induced by non-alcoholic fatty liver disease causes peri-interventional complications in morbidly obese patients. We determined the performance of transient elastography (TE), acoustic radiation force impulse (ARFI) imaging, and enhanced liver fibrosis (ELF) score for fibrosis detection in bariatric patients. Patients and Methods: 41 patients (median BMI 47 kg/m2) underwent 14-day low-energy diets to improve conditions prior to bariatric surgery (day 0). TE (M and XL probe), ARFI, and ELF score were performed on days -15 and -1 and compared with intraoperative liver biopsies (NAS staging). Results: Valid TE and ARFI results at day -15 and -1 were obtained in 49%/88%and 51%/90%of cases, respectively. High skin-to-liver-capsule distances correlated with invalid TE measurements. Fibrosis of liver biopsies was staged as F1 and F3 in n = 40 and n = 1 individuals. However, variations (median/range at d-15/-1) of TE (4.6/2.6–75 and 6.7/2.9–21.3 kPa) and ARFI (2.1/0.7–3.7 and 2.0/0.7–3.8 m/s) were high and associated with overestimation of fibrosis. The ELF score correctly classified 87.5%of patients. Conclusion: In bariatric patients, performance of TE and ARFI was poor and did not improve after weight loss. The ELF score correctly classified the majority of cases and should be further evaluated.

Background: Skinfold thickness (ST), waist circumference (WC) and hip circumference (HC) measurements are simple methods for assessing fat tissue at defined body parts. We examined these parameters in a cohort of healthy children and adolescents in Leipzig. Our study provides current percentile curves for biceps, triceps, subscapular and iliac crest ST, plus WC, HC, Waist-to-Hip Ratio and Waist-to-Height Ratio. Materials and methods: 6,344 visits were recorded involving 2,363 individuals from 3 to 16 years in age. Continuous age- and gender-related percentiles (3rd, 10th, median, 90th, 97th percentiles) were estimated using Cole's LMS method. Results: For biceps and triceps ST, boys show a peak at the beginning of adolescence with a subsequent decrease, while percentile values among girls rise across the age range. Subscapular and iliac crest percentiles also show increasing curves with disproportionately high values for P90 and P97. Boys show higher values of WC, girls have higher levels of HC. WC and HC median percentiles constantly increase in both sexes with a plateau at the age of 16 for girls. Conclusion: Trends for all parameters of body fat are in line with other national and international studies. Unlike the KiGGS study, our study provides circumference data across the whole of our age range, i.e. from 3-16 years.:I. Abkürzungsverzeichnis 1. Vorbemerkung 2. Wissenschaftlicher Hintergrund 2.1. Übergewicht und Adipositas im Kindes- und Jugendalter 2.2. Bestimmung des Körperfettanteils bei Kindern und Jugendlichen 2.3. Die Bedeutung kindlichen Übergewichts und dessen Folgeschäden 2.4. Assoziation von Körperfettparametern und kardiovaskulären Risikofaktoren im Fokus 2.5. Anthropometrische Referenzwerte für Kinder und Jugendliche in Deutschland 3. Fragestellung 4. Publikation 5. Zusammenfassung der Arbeit 6. Literaturverzeichnis II. Anlagen 1. Abbildungen 2. Tabellen 3. Formeln nach Slaughter zur Abschätzung des Körperfettanteils III. Darstellung des eigenen Beitrags IV. Erklärung über die eigenständige Abfassung der Arbeit VI. Danksagung

Adiposity has been linked to impaired respiratory function in adults but whether the distribution of adipose tissue has a differential effect on pulmonary function is still uncertain. Moreover, in children, the relationship between adiposity and lung dysfunction is not clearly understood. A two-stage multivariate analysis was conducted using data from 5604 Canadians aged 6 to 79 years who participated in the Canadian Health Measures Survey (CHMS). The associations of various anthropometric and skinfold measures with lung function were examined separately in adults and children. After adjustment of covariates, waist circumference and subscapular skinfold thickness showed the strongest inverse associations with FVC and FEV1 in men. In women, BMI and sum of five skinfolds had the largest impact on pulmonary function. FVC and FEV1 in boys were most affected by waist-to-hip ratio and triceps skinfold. In girls, adiposity was not linked to the lung function testing variables. Adiposity measures have differing effects on respiratory function depending on age and sex group.

The purpose of this study was to test whether a relationship exists between adiposity and functional capacity. A moderate negative correlation was found between adiposity and functional capacity. This indicates that as adiposity increases, functional capacity decreases.

Exposure to certain stressors during a sensitive period around puberty can lead to enduring effects on an animal’s response to estradiol. In estradiol-influenced behaviors, such as sexual receptivity, hippocampal-dependent learning and memory, depression-like behavior, and anxiety-like behaviors, exposure to a peripubertal stressor such as shipping stress or an injection of lipopolysaccharide (LPS) can eliminate or even reverse the normal response to estradiol. In addition to regulating these behaviors, estradiol play a role in the regulation of body weight. While some of the previous studies touched on short-term effects on body weight, no systemic long-term study of the effects of a peripubertal stressor on body weight, particularly without interruption by ovariectomy, have been undertaken. This paper introduces a hypothesis that proposes that increased adiposity following exposure to a peripubertal stressor leads to the changes to estrogen-dependent behaviors through altered levels of estrogens and changes to estrogen receptors. The first chapter examines body weight data collected during studies with other aims, and then proposes an experiment to test whether either of two peripubertal stressors results in increased weight gain and body weight. The following chapter proposes further experiments designed to determine the proximate mechanisms leading to weight gain following peripubertal stressors and the role of diet on weight gain. The final chapter proposes experiments to test the effects of adiposity on peripheral levels of testosterone, aromatase, estradiol, and estrone; central levels of estradiol and estrone; and estrogen receptors in the brain.

BACKGROUND: Metabolic syndrome, elevated blood pressure (BP), elevated cholesterol and type 2 diabetes mellitus are health conditions that increase cardiometabolic risk (CMR). Sleep, physical activity, diet, are modifiable risk factors for the prevention of cardiometabolic disorders. Dietary fiber which is associated with higher fruit and vegetable intakes is known to lower the effects of obesity-related health issues. Further, these foods have an abundance of beneficial vitamins and minerals as well as low energy density. There is controversial, however, regarding the effect of fruit juice intake on CMR, particularly due to its lower fiber content. The objectives of this research were to estimate the effect of intakes of whole fruit and fruit juice on CMR, including effects on Body Mass Index (BMI), overweight/obesity, hypertension/prehypertension, lipid, and blood glucose levels. METHODS: The National Heart, Lung, and Blood Institute’s National Growth and Health Study (NGHS) cohort of white and black girls ages 9-10 years at baseline participated in a 10-year longitudinal study. Cardiometabolic outcomes included repeated measures of adiposity (e.g., body mass index (BMI)), and blood pressure, as well as laboratory measures such as fasting glucose and lipid levels. Linear regression and logistic regression were used to assess the association of fruit intake and fruit juice intake on CMR, while adjusting for age, race, tv/video, total vegetables, lean meat, and % calories from fat. Statistical Analysis Software (SAS Institute 15.2) analysis of data was performed. Results were considered statistically significant when p-value was <0.05. RESULTS: For girls in NGHS, BMI at the end of adolescence (ages 17-20 years) averaged to 21.3 kg/m2 for those who ate ≥0.75 cups of fruit and 22.1 kg/m2 for girls who ate <0.25 cups fruit. Similarly, girls with higher fruit juice consumption (≥0.75 cup-equivalents of juice per day) had a statistically significantly lower BMI than those with the lowest juice intake (<0.25 cup-eq/day). For each additional cup of whole fruit consumed on average per day between the ages of 9-17 was associated with 0.18 kg/m2 lower BMI (p<0.0001), after adjusting for age, race, tv/video viewing, total vegetable, lean meat intake, and % calories from fat. Adolescent girls (17 years or older) who drank < 0.25 or 0.25 - < 0.5 cup equivalent fruit juice were 1.60 or 1.63 (respectively) times more likely to become overweight (p-value 0.0005). Neither fruit intake nor fruit juice was associated with elevated fasting glucose risk or with high LDL risk. Whole fruit consumption was associated with a beneficial effect on HDL-cholesterol. Those with low whole fruit intake had a 1.42-fold increased risk of low HDL. CONCLUSIONS: These results indicate that 100% fruit juice and whole fruit consumption are both associated with beneficial effects on BMI and blood pressure among adolescent girls, suggesting that these foods may aid in the prevention of obesity and hypertension in the early adult years. KEY WORDS: adolescents, adiposity, body mass index, blood pressure, cardiometabolic health, dietary fiber, dyslipidemia, juice, glucose, metabolic syndrome, obesity, fruit.

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