Dietetics and Clinical Nutrition Commons^™

Activation Of The Innate Immune System In Children With Irritable Bowel Syndrome Evidenced By Increased Fecal Human Β-Defensin-2, Robert J Shulman, Sridevi Devaraj, Margaret Heitkemper

Children’s Nutrition Research Center Staff Publications

Background & aims: The role of the innate immune system in functional gastrointestinal pain disorders is unclear. We investigated the role of β-defensin-2 and gut permeability in childhood irritable bowel syndrome (IBS) and functional abdominal pain (FAP) symptom generation.

Methods: Fecal β-defensin-2 (and in a subset, gut permeability) was measured in children with IBS (n = 116), FAP (n = 33), and healthy control (HC) children (n = 72). IBS and FAP patients were recruited from tertiary and primary care, and HCs were recruited from primary care.

Results: β-defensin-2 concentration was greater in children with IBS (P = .003) and …

Intermittent Bolus Compared With Continuous Feeding Enhances Insulin And Amino Acid Signaling To Translation Initiation In Skeletal Muscle Of Neonatal Pigs, Agus Suryawan, Samer W El-Kadi, Hanh V Nguyen, Marta L Fiorotto, Teresa A Davis

Children’s Nutrition Research Center Staff Publications

Background: Nutrition administered as intermittent bolus feeds rather than continuously promotes greater protein synthesis rates in skeletal muscle and enhances lean growth in a neonatal piglet model. The molecular mechanisms responsible remain unclear.

Objectives: We aimed to identify the insulin- and/or amino acid-signaling components involved in the enhanced stimulation of skeletal muscle by intermittent bolus compared to continuous feeding in neonatal pigs born at term.

Methods: Term piglets (2-3 days old) were fed equal amounts of sow milk replacer [12.8 g protein and 155 kcal/(kg body weight · d)] by orogastric tube as intermittent bolus meals every 4 hours (INT) …

Multisite Pain Is Highly Prevalent In Children With Functional Abdominal Pain Disorders And Is Associated With Increased Morbidity, Bruno P Chumpitazi, Tonya M Palermo, John M Hollier, Mariella M Self, Danita Czyzewski, Erica M Weidler, Margaret Heitkemper, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Objectives: To characterize the types of multisite pain experienced by children with functional abdominal pain disorders (FAPDs) and to examine differences in psychosocial distress, functional disability, and health-related quality of life in children with multisite pain vs abdominal pain alone.

Study design: Cross-sectional study of children ages 7-17 years (n = 406) with pediatric Rome III FAPDs recruited from both primary and tertiary care between January 2009 and June 2018. Subjects completed 14-day pain and stool diaries, as well as validated questionnaires assessing abdominal and nonabdominal pain symptoms, anxiety, depression, functional disability, and health-related quality of life.

Results: In total, …

Daily Energy Expenditure Through The Human Life Course, Herman Pontzer, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G Camps, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marjije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Teresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia Loechl, Amy H Luke, Jennifer Rood, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

Total daily energy expenditure (“total expenditure”, MJ/d) reflects daily energy needs and is a critical variable in human health and physiology, yet it is unclear how daily expenditure changes over the life course. Here, we analyze a large, globally diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 yr. We show that total expenditure is strongly related to fat free mass in a power-law manner and identify four distinct metabolic life stages. Fat free mass-adjusted daily expenditure accelerates rapidly in neonates (0-1yr) to ~46% above adult values at …

Simple Energy Balance Or Microbiome For Childhood Obesity Prevention?, Tom Baranowski, Kathleen J Motil

Children’s Nutrition Research Center Staff Publications

Obesity prevention interventions generally have either not worked or had effects inadequate to mitigate the problem. They have been predicated on the simple energy balance model, which has been severely questioned by biological scientists. Numerous other etiological mechanisms have been proposed, including the intestinal microbiome, which has been related to childhood obesity in numerous ways. Public health research is needed in regard to diet and the microbiome, which hopefully will lead to effective child obesity prevention.

Family-Based Obesity Prevention Interventions Among Hispanic Children And Families: A Scoping Review, Erica G Soltero, Armando Peña, Veronica Gonzalez, Edith Hernandez, Guisela Mackey, Chishinga Callender, Jayna M Dave, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

This scoping review examined intervention and sample characteristics of family-based obesity prevention interventions among Hispanic youth. This review also examined the degree to which existing interventions were culturally-adapted, acknowledged social determinants of health (SDoH), and collaborated with community stakeholders. A comprehensive search across Medline Ovid, Embase, Scopus, PsycInfo, and Pubmed was used to identify 13 studies primarily based in the U.S. (92.3%). Data was extracted by two independent reviewers. Most used a randomized control trial design (69.2%), a behavior change theory (84.6%), and reported moderate to high (≥70%) retention (69.2%). Studies targeted improvements in physical activity (69.2%) and fruit and …

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown

Faculty, Staff and Students Publications

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the

METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near

RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers …

Feasibility And Efficacy Of The "Funpals Playgroup" Intervention To Improve Toddler Dietary And Activity Behaviors: A Pilot Randomized Controlled Trial, Aliye B Cepni, Ashley Taylor, Christine Crumbley, Debbe Thompson, Nancy E Moran, Norma Olvera, Daniel P O'Connor, Katherine R Arlinghaus, Craig A Johnston, Tracey A Ledoux

Children’s Nutrition Research Center Staff Publications

This study evaluated the feasibility and effects of the Families Understanding Nutrition and Physically Active Lifestyles (FUNPALs) Playgroup on toddler (12–36-month-old) diet and activity behaviors. Parent–toddler dyads were recruited from disadvantaged communities and randomly assigned to receive 10-weekly sessions of the FUNPALs Playgroup (n = 24) or dose-matched health education control group (n = 26). FUNPALs Playgroups involved physical and snack activities, delivery of health information, and positive parenting coaching. The control group involved group health education for parents only. Process outcomes (e.g., retention rate, fidelity) and focus groups determined feasibility and perceived effects. To evaluate preliminary effects, …

Later Sleep Timing Predicts Accelerated Summer Weight Gain Among Elementary School Children: A Prospective Observational Study, Jennette P Moreno, Javad Razjouyan, Houston Lester, Hafza Dadabhoy, Mona Amirmazaheri, Layton Reesor-Oyer, Teresia M O'Connor, Daphne C Hernandez, Bijan Najafi, Candice A Alfano, Stephanie J Crowley, Debbe Thompson, Tom Baranowski

Children’s Nutrition Research Center Staff Publications

Objectives and background: Social demands of the school-year and summer environment may affect children's sleep patterns and circadian rhythms during these periods. The current study examined differences in children's sleep and circadian-related behaviors during the school-year and summer and explored the association between sleep and circadian parameters and change in body mass index (BMI) during these time periods.

Methods: This was a prospective observational study with 119 children ages 5 to 8 years with three sequential BMI assessments: early school-year (fall), late school-year (spring), and beginning of the following school-year in Houston, Texas, USA. Sleep midpoint, sleep duration, variability of …

Associations Between Screen-Based Activities, Physical Activity, And Dietary Habits In Mexican Schoolchildren, Erica G Soltero, Alejandra Jáuregui, Edith Hernandez, Simón Barquera, Edtna Jáuregui, Juan Ricardo López-Taylor, Luis Ortiz-Hernández, Lucie Lévesque, Rebecca E Lee

Children’s Nutrition Research Center Staff Publications

Screen-based activities are associated with increased risk of obesity and contribute to physical inactivity and poor dietary habits. The primary aim of this study was to examine the associations among screen-based activities, physical activity, and dietary habits in school-aged children in Guadalajara, Puerto Vallarta, and Mexico City, Mexico. The secondary aim was to examine these associations across sex. The School Physical Activity and Nutrition survey was used to assess screen-based activities (TV watching, video game use, computer use), physical activity, and dietary habits. Organized activity/sports participation, unhealthy dietary habits, and household income were correlated with screen-based activities. While TV watching …

Subchronic Tolerance Trials Of Graded Oral Supplementation With Phenylalanine Or Serine In Healthy Adults, Naoki Miura, Hideki Matsumoto, Luc Cynober, Patrick J Stover, Rajavel Elango, Motoni Kadowaki, Dennis M Bier, Miro Smriga

Children’s Nutrition Research Center Staff Publications

Phenylalanine and serine are amino acids used in dietary supplements and nutritional products consumed by healthy consumers; however, the safe level of phenylalanine or serine supplementation is unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral phenylalanine and oral serine. Healthy male adults (n = 60, 38.2 ± 1.8y) completed graded dosages of either phenylalanine or serine supplement (3, 6, 9 and 12 g/d) for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, …

Clinical Characterization Of Pediatric Gastroparesis Using A Four-Hour Gastric Emptying Scintigraphy Standard, Sharon Wolfson, Zoe Wilhelm, Antone R Opekun, Robert Orth, Robert J Shulman, Bruno P Chumpitazi

Children’s Nutrition Research Center Staff Publications

Objectives: Four-hour gastric emptying scintigraphy (GES) is the recommended method to identify both adult and childhood gastroparesis (GP). Previous pediatric studies have, however, not used this standard. We sought to determine the characteristics and outcomes of children versus adolescents with GP using the 4-hour GES evaluation.

Methods: We performed a retrospective chart review of pediatric patients diagnosed with GP by 4-hour GES (>10% retention at 4 hours). Demographics, body mass index, GP-related symptoms, comorbidities, etiologies, therapies (eg, medications), healthcare utilization, and response to therapy were captured systematically. Symptoms were compared from the initial versus last gastroenterology visit. Outcomes were …

Defining Vdr Expression In The Brain Using A Novel Vdrcre Mouse, Hailan Liu, Yang He, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Yong Xu, Stephanie Sisley

Children’s Nutrition Research Center Staff Publications

Vitamin D action has been linked to several diseases regulated by the brain including obesity, diabetes, autism, and Parkinson’s. However, the location of the vitamin D receptor (VDR) in the brain is not clear due to conflicting reports. We found that two antibodies previously published as specific in peripheral tissues are not specific in the brain. We thus created a new knockin mouse with cre recombinase expression under the control of the endogenous VDR promoter (VDRCre). We demonstrated that the cre activity in the VDRCre mouse brain (as reported by a cre-dependent tdTomato expression) is highly overlapping with endogenous VDR …

Cell Lineage Tracing Links Erα Loss In Erbb2-Positive Breast Cancers To The Arising Of A Highly Aggressive Breast Cancer Subtype, Yunfeng Ding, Yonghong Liu, Dong-Kee Lee, Zhangwei Tong, Xiaobin Yu, Yi Li, Yong Xu, Rainer B Lanz, Bert W O'Malley, Jianming Xu

Children’s Nutrition Research Center Staff Publications

HER2-positive (HER2+) breast cancers (BrCs) contain approximately equal numbers of ERα+HER2+ and ERα−HER2+ cases. An enduring obstacle is the unclear cell lineage-related characteristics of these BrCs. Although ERα+HER2+ BrCs could lose ERα to become ERα−HER2+ BrCs, direct evidence is missing. To investigate ERα dependencies and their implications during BrC growth and metastasis, we generated ERαCreRFP-T mice that produce an RFP-marked ERα+ mammary gland epithelial cell (MGEC) lineage. RCAS virus-mediated expression of Erbb2, a rodent Her2 homolog, first produced comparable numbers of ERα+RFP+Erbb2+ and ERα−RFP−Erbb2+ MGECs. Early hyperplasia developed mostly from ERα+RFP+Erbb2+ cells and ERα−RFP−Erbb2+ cells in these lesions were rare. …

Consumption Of High-Fructose Corn Syrup Compared With Sucrose Promotes Adiposity And Increased Triglyceridemia But Comparable Nafld Severity In Juvenile Iberian Pigs, Magdalena Maj, Brooke Harbottle, Payton A Thomas, Gabriella V Hernandez, Victoria A Smith, Mark S Edwards, Rob K Fanter, Hunter S Glanz, Chad Immoos, Douglas G Burrin, Tasha M Santiago-Rodriguez, Michael R La Frano, Rodrigo Manjarín

Children’s Nutrition Research Center Staff Publications

Background: Fructose consumption has been linked to nonalcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) compared with sucrose in pediatric NAFLD has not been investigated.

Objectives: We tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, SCFA production, and microbial diversity.

Methods: Iberian pigs, 53-d-old and pair-housed in pens balanced for weight and sex, were randomly assigned to receive a mash diet top-dressed with increasing amounts of sucrose (SUC; n = …

Dietary Factors And Gastric Intestinal Metaplasia Risk Among Us Veterans, Mimi C Tan, Niharika Mallepally, Quynh Ho, Yan Liu, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Studies on diet and gastric intestinal metaplasia (GIM) risk are lacking in US populations.

AIM: To determine the associations of dietary factors and risk of GIM among a US population with typical American diet.

METHODS: We analyzed data from a cross-sectional study of veterans attending primary care and endoscopy clinics at the Houston VA Medical Center. Patients completed a 110-item Block Food Frequency Questionnaire then underwent upper endoscopy with gastric mapping biopsies. We compared cases defined by GIM on ≥ 1 non-cardia gastric biopsy to controls without GIM. Associations of dietary factors and GIM were estimated using logistic regression …

Blood N-3 Fatty Acid Levels And Total And Cause-Specific Mortality From 17 Prospective Studies, William S Harris, Nathan L Tintle, Fumiaki Imamura, Frank Qian, Andres V Ardisson Korat, Matti Marklund, Luc Djoussé, Julie K Bassett, Pierre-Hugues Carmichael, Yun-Yu Chen, Yoichiro Hirakawa, Leanne K Küpers, Federica Laguzzi, Maria Lankinen, Rachel A Murphy, Cécilia Samieri, Mackenzie K Senn, Peilin Shi, Jyrki K Virtanen, Ingeborg A Brouwer, Kuo-Liong Chien, Gudny Eiriksdottir, Nita G Forouhi, Johanna M Geleijnse, Graham G Giles, Vilmundur Gudnason, Catherine Helmer, Allison Hodge, Rebecca Jackson, Kay-Tee Khaw, Markku Laakso, Heidi Lai, Danielle Laurin, Karin Leander, Joan Lindsay, Renata Micha, Jaako Mursu, Toshiharu Ninomiya, Wendy Post, Bruce M Psaty, Ulf Risérus, Jennifer G Robinson, Aladdin H Shadyab, Linda Snetselaar, Aleix Sala-Vila, Yangbo Sun, Lyn M Steffen, Michael Y Tsai, Nicholas J Wareham, Alexis C Wood, Jason H Y Wu, Frank Hu, Qi Sun, David S Siscovick, Rozenn N Lemaitre, Dariush Mozaffarian, Fatty Acids And Outcomes Research Consortium (Force)

Children’s Nutrition Research Center Staff Publications

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Meal-Induced Symptoms In Children With Dyspepsia-Relationships To Sex And The Presence Of Gastroparesis, Liz Febo-Rodriguez, Bruno P Chumpitazi, Salma Musaad, Andrew C Sher, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Objectives: To test the hypothesis that in children with dyspepsia, prospective symptom severity following ingestion of a meal would correlate with percent gastric retention, and those ultimately diagnosed with gastroparesis would report worse symptoms.

Study design: Prospective, single-center study with 104 children with dyspepsia completing a prospective dyspepsia symptom questionnaire before and after eating a standardized Tougas meal during gastric emptying scintigraphy. Main outcomes included correlation between gastric retention and symptoms and comparison of symptom severity between those with and without gastroparesis.

Results: Fifty-two children (50%) had gastroparesis (gastroparesis: 12.5 ± 2.9 years, 65% female; nongastroparesis: 13.0 ± 2.9 years, …

Prematurity Blunts The Insulin- And Amino Acid-Induced Stimulation Of Translation Initiation And Protein Synthesis In Skeletal Muscle Of Neonatal Pigs, Marko Rudar, Jane K Naberhuis, Agus Suryawan, Hanh V Nguyen, Barbara Stoll, Candace C Style, Mariatu A Verla, Oluyinka O Olutoye, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Children’s Nutrition Research Center Staff Publications

Extrauterine growth restriction in premature infants is largely attributed to reduced lean mass accretion and is associated with long-term morbidities. Previously, we demonstrated that prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in skeletal muscle of neonatal pigs. The objective of the current study was to determine whether the blunted feeding response is mediated by reduced responsiveness to insulin, amino acids, or both. Pigs delivered by cesarean section preterm (PT; 103 days,

Perfluorooctanoic Acid (Pfoa) Or Perfluorooctane Sulfonate (Pfos) And Dna Methylation In Newborn Dried Blood Spots In The Upstate Kids Cohort, Sonia L Robinson, Xuehuo Zeng, Weihua Guan, Rajeshwari Sundaram, Pauline Mendola, Diane L Putnick, Robert A Waterland, Chathura J Gunasekara, Kurunthachalam Kannan, Chongjing Gao, Erin M Bell, Edwina H Yeung

Children’s Nutrition Research Center Staff Publications

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent organic pollutants which may alter prenatal development, potentially through epigenetic modifications. Prior studies examining PFOS/PFOA and DNA methylation have relatively few subjects (n < 200) and inconsistent results. We examined relations of PFOA/PFOS with DNA methylation among 597 neonates in the Upstate KIDS cohort study. PFOA/PFOS were quantified in newborn dried blood spots (DBS) using high-performance liquid chromatography/tandem mass spectrometry. DNA methylation was measured using the Infinium MethylationEPIC BeadChip with DNA extracted from DBS. Robust linear regression was used to examine the associations of PFOA/PFOS with DNA methylation at individual CpG sites. Covariates included sample plate, estimated cell type, epigenetically derived ancestry, infant sex and plurality, indicators of maternal socioeconomic status, and prior pregnancy loss. In supplemental analysis, we restricted the analysis to 2242 CpG sites previously identified as Correlated Regions of Systemic Interindividual Variation (CoRSIVs) which include metastable epialleles. At FDR90th percentile was related to DNA methylation at cg15557840, near SCRT2, SRXN1; PFOS>90th percentile was related to 2 CpG sites in a sex-specific manner (cg19039925 in GVIN1 in boys and cg05754408 in ZNF26 in girls). When analysis was restricted to CoRSIVs, log-scaled, continuous PFOS concentration was related to DNA methylation at cg03278866 within PTBP1. In conclusion, there was limited evidence of an association between high concentrations of PFOA/PFOS and DNA methylation in newborn DBS in the Upstate KIDS cohort. These …

Metabolic Flexibility Across The Spectrum Of Glycemic Regulation In Youth, Fida Bacha, Sara Klinepeter Bartz, Maurice Puyau, Anne Adolph, Susan Sharma

Children’s Nutrition Research Center Staff Publications

BACKGROUNDMetabolic flexibility (MF) refers to the relative ability to utilize lipid and carbohydrate substrates and to transition between them. It is not clear whether MF is impaired in obese youth and what the determining factors are.METHODSWe investigated the determinants of MF (increased respiratory exchange ratio [ΔRER] under insulin-stimulated conditions) in pubertal youth (n = 104; 15.6 ± 1.8 years) with obesity across the spectrum of glucose tolerance compared with normal weight (NW) controls, including body composition (fat-free mass [FFM], %body fat), visceral adipose fat (VAT) (MRI), glycemia, and insulin sensitivity (IS) [3-hour hyperinsulinemic-euglycemic clamp with measurement of lipolysis ([2H5] glycerol), …

Assessment Of The Gut Bacterial Microbiome And Metabolome Of Girls And Women With Rett Syndrome, Santosh Thapa, Alamelu Venkatachalam, Nabeel Khan, Mohammed Naqvi, Miriam Balderas, Jessica K Runge, Anthony Haag, Kathleen M Hoch, Daniel G Glaze, Ruth Ann Luna, Kathleen J Motil

Children’s Nutrition Research Center Staff Publications

Background: Gastrointestinal problems affect the health and quality of life of individuals with Rett syndrome (RTT) and pose a medical hardship for their caregivers. We hypothesized that the variability in the RTT phenotype contributes to the dysbiosis of the gut microbiome and metabolome in RTT, predisposing these individuals to gastrointestinal dysfunction.

Objectives: We characterized the gut bacterial microbiome and metabolome in girls and young women with RTT (n = 44) and unaffected controls (n = 21), and examined the relation between the composition of the microbiome and variations in the RTT phenotype.

Methods: Demographics and clinical information, including growth and …

Gut Microbiota Profiles Of Young South Indian Children: Child Sex-Specific Relations With Growth, Nirupama Shivakumar, Ambily Sivadas, Sarita Devi, Farook Jahoor, John Mclaughlin, Craig P Smith, Anura V Kurpad, Arpita Mukhopadhyay

Children’s Nutrition Research Center Staff Publications

Gut microbiota has been implicated as a modifier of childhood growth. Here, 16S rRNA sequencing-based fecal microbiota profiles of 18-24 month old Indian children were evaluated (n = 41), in relation to their anthropometric parameters, intestinal permeability, body composition and total energy expenditure. Pathway analyses were conducted to assess microbial functions related to stunting, underweight and wasting. The fecal microbiota was enriched in Prevotella 9, Bifidobacterium and Escherichia-Shigella. Weight, weight-for-age Z-scores (WAZ) and weight-for-length Z-scores (WLZ), along with age, acted as covariates of microbiota variation specifically in boys (n = 23). Bifidobacterium longum subsp longum abundance was positively associated with …

Tph2 In The Dorsal Raphe Nuclei Regulates Energy Balance In A Sex-Dependent Manner, Hailan Liu, Chunmei Wang, Meng Yu, Yongjie Yang, Yang He, Hesong Liu, Chen Liang, Longlong Tu, Nan Zhang, Lina Wang, Julia Wang, Feng Liu, Fang Hu, Yong Xu

Children’s Nutrition Research Center Staff Publications

AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors a similar amount of TPH2+ cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female …

Modeling Age-Dependent Developmental Changes In The Expression Of Genes Involved In Citrulline Synthesis Using Pig Enteroids, Mahmoud A Mohammad, Inka C Didelija, Barbara Stoll, Douglas G Burrin, Juan C Marini

Children’s Nutrition Research Center Staff Publications

metabolism of citrulline and arginine are well characterized. Enteroids, a novel ex-vivo model that recreates the three-dimensional structure of the intestinal crypt-villus unit, have shown to replicate molecular and physiological profiles of the intestinal segment from where they originated ("location memory").

Objective: The present study tested the hypothesis that enteroids recapitulate the developmental changes observed in vivo regarding citrulline production in pigs ("developmental memory").

Methods: Preterm (10- and 5-d preterm) and term pigs at birth, together with 7- and 35-d-old pigs were studied. Gene expression was measured in jejunal samples and in enteroids derived from this segment. Whole body citrulline …

Type 1 Doing Well: Pilot Feasibility And Acceptability Study Of A Strengths-Based Mhealth App For Parents Of Adolescents With Type 1 Diabetes, Marisa E Hilliard, Viena T Cao, Sahar S Eshtehardi, Charles G Minard, Rana Saber, Debbe Thompson, Lefkothea P Karaviti, Barbara J Anderson

Children’s Nutrition Research Center Staff Publications

Background: We evaluated the feasibility and acceptability of a pilot behavioral intervention delivered to parents of adolescents with type 1 diabetes (T1D) via mobile-friendly web app. The Type 1 Doing Well app aimed to promote supportive family diabetes management by helping parents recognize and reinforce teens' positive diabetes-related behaviors ("strengths").

Methods: Parents (n = 80, 74% recruitment) of adolescents (age range = 12-17 years, M = 15.3 ± 1.5 years, 59% female, 56% insulin pump, M hemoglobin A1c (HbA1c) = 9.0% ± 2.1%) were randomized 2:1 to intervention or control (i.e., usual medical care with or without app) for …

Β-Cell Impairment And Clinically Meaningful Alterations In Glycemia In Obese Youth Across The Glucose Tolerance Spectrum, Joon Young Kim, Hala Tfayli, Fida Bacha, Sojung Lee, Nour Gebara, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Background/aims: In obese youth, it is not clear what degree of β-cell impairment translates to glucose dysregulation commensurate with shifts from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes. We aimed to investigate the quantitative relationship between β-cell (clamp-measured disposition index [DI]) and OGTT glucose area under the curve (G-AUC) in obese youth across the spectrum of glucose tolerance.

Methods: Data from 152 youth (58 African-American [AA] and 94 American-White [AW]; 73 NGT, 48 IGT, and 31 type 2 diabetes) who completed a 3-h hyperinsulinemic (80 mu/m2/min)-euglycemic clamp, and a 2-h hyperglycemic (225 mg/dL) clamp …

Fat And Fat-Free Mass Index References In Children And Young Adults: Assessments Along Racial And Ethnic Lines, Roman J Shypailo, William W Wong

Children’s Nutrition Research Center Staff Publications

Background: Fat-free mass index (FFMI) and fat mass index (FMI) are superior to BMI and fat percentage in evaluating nutritional status. However, existing references fail to account for racial/ethnic differences in body composition among children.

Objectives: Our goal was to produce age-based normative references for FFMI and FMI in children for specific racial/ethnic groups.

Methods: Body composition, weight, and height were measured in 1122 normal healthy children aged 2-21 y. Bone mineral content measured by DXA, total body water by deuterium dilution, and total body potassium by whole-body γ counting were combined to calculate fat-free mass (FFM) and fat mass …

Profound And Redundant Functions Of Arcuate Neurons In Obesity Development, Canjun Zhu, Zhiying Jiang, Yuanzhong Xu, Zhao-Lin Cai, Qingyan Jiang, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Qi Wu, Gang Shu, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

The current obesity epidemic faces a lack of mechanistic insights. It is known that the acute activity changes of a growing number of brain neurons rapidly alter feeding behaviour; however, how these changes translate to obesity development and the fundamental mechanism underlying brain neurons in controlling body weight remain elusive. Here, we show that chronic activation of hypothalamic arcuate GABAergic (GABA

Estrogen Receptor-Α Expressing Neurons In The Ventrolateral Vmh Regulate Glucose Balance, Yanlin He, Pingwen Xu, Chunmei Wang, Yan Xia, Meng Yu, Yongjie Yang, Kaifan Yu, Xing Cai, Na Qu, Kenji Saito, Julia Wang, Ilirjana Hyseni, Matthew Robertson, Badrajee Piyarathna, Min Gao, Sohaib A Khan, Feng Liu, Rui Chen, Cristian Coarfa, Zhongming Zhao, Qingchun Tong, Zheng Sun, Yong Xu

Children’s Nutrition Research Center Staff Publications

Brain glucose-sensing neurons detect glucose fluctuations and prevent severe hypoglycemia, but mechanisms mediating functions of these glucose-sensing neurons are unclear. Here we report that estrogen receptor-α (ERα)-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) can sense glucose fluctuations, being glucose-inhibited neurons (GI-ERαvlVMH) or glucose-excited neurons (GE-ERαvlVMH). Hypoglycemia activates GI-ERαvlVMH neurons via the anoctamin 4 channel, and inhibits GE-ERαvlVMH neurons through opening the ATP-sensitive potassium channel. Further, we show that GI-ERαvlVMH neurons preferentially project to the medioposterior arcuate nucleus of the hypothalamus (mpARH) and GE-ERαvlVMH neurons preferentially project to the dorsal Raphe nuclei (DRN). Activation of ERαvlVMH …