Dietetics and Clinical Nutrition Commons^™

The Shape Of The Oral Glucose Tolerance Test-Glucose Response Curve In Islet Cell Antibody-Positive Vs -Negative Obese Youth Clinically Diagnosed With Type 2 Diabetes, Joon Young Kim, Hala Tfayli, Fida Bacha, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

BACKGROUND: The oral glucose tolerance test (OGTT)-glucose response curves (GRCs; incessant increase, monophasic, and biphasic) reflect insulin sensitivity and β-cell function, being worse in the former and superior in the latter. Here, we examined if the OGTT-GRC pattern is worse in obese antibody (glutamic acid decarboxylase 65-kDa [GAD65] and insulinoma-associated protein-2 [IA-2])-positive (Ab

METHODS: Forty-seven obese youth, 15 Ab

RESULTS: Incessant increase OGTT-GRC is the most frequent curve type and is three-fold higher in Ab

CONCLUSION: Severe insulin deficiency, a characteristic of type 1 diabetes, seems to be related to higher prevalence of incessant increase in Ab

Restoration Of The Molecular Clock Is Tumor Suppressive In Neuroblastoma, Myrthala Moreno-Smith, Giorgio Milazzo, Ling Tao, Baharan Fekry, Bokai Zhu, Mahmoud A Mohammad, Simone Di Giacomo, Roshan Borkar, Karthik Reddy Kami Reddy, Mario Capasso, Sanjeev A Vasudevan, Pavel Sumazin, John Hicks, Nagireddy Putluri, Giovanni Perini, Kristin Eckel-Mahan, Thomas P Burris, Eveline Barbieri

Children’s Nutrition Research Center Staff Publications

MYCN activation is a hallmark of advanced neuroblastoma (NB) and a known master regulator of metabolic reprogramming, favoring NB adaptation to its microenvironment. We found that the expression of the main regulators of the molecular clock loops is profoundly disrupted in MYCN-amplified NB patients, and this disruption independently predicts poor clinical outcome. MYCN induces the expression of clock repressors and downregulates the one of clock activators by directly binding to their promoters. Ultimately, MYCN attenuates the molecular clock by suppressing BMAL1 expression and oscillation, thereby promoting cell survival. Reestablishment of the activity of the clock activator RORα via its genetic …

Defining The Relative Role Of Insulin Clearance In Early Dysglycemia In Relation To Insulin Sensitivity And Insulin Secretion: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Gautam Ramesh, Stephen S Rich, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi

Children’s Nutrition Research Center Staff Publications

Insulin resistance and insufficient insulin secretion are well-recognized contributors to type 2 diabetes. A potential role of reduced insulin clearance has been suggested, but few studies have investigated the contribution of insulin clearance while simultaneously examining decreased insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in a cohort of 353 non-Hispanic White and African American individuals recruited in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). Participants underwent oral glucose tolerance tests from which insulin sensitivity, insulin secretion, insulin clearance, and disposition index were calculated. Regression models examined the individual and joint contributions …

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 …

Deciphering An Agrp-Serotoninergic Neural Circuit In Distinct Control Of Energy Metabolism From Feeding, Yong Han, Guobin Xia, Dollada Srisai, Fantao Meng, Yanlin He, Yali Ran, Yang He, Monica Farias, Giang Hoang, István Tóth, Marcelo O Dietrich, Miao-Hsueh Chen, Yong Xu, Qi Wu

Children’s Nutrition Research Center Staff Publications

Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4RdlDRN neurons …

Gene Expression Analysis Of Environmental Temperature And High-Fat Diet-Induced Changes In Mouse Supraclavicular Brown Adipose Tissue, Yufeng Shi, Honglei Zhai, Sharon John, Yi-Ting Shen, Yali Ran, Giang Hoang, Miao-Hsueh Chen

Children’s Nutrition Research Center Staff Publications

Obesity, a dysregulation of adipose tissue, is a major health risk factor associated with many diseases. Brown adipose tissue (BAT)-mediated thermogenesis can potentially regulate energy expenditure, making it an attractive therapeutic target to combat obesity. Here, we characterize the effects of cold exposure, thermoneutrality, and high-fat diet (HFD) feeding on mouse supraclavicular BAT (scBAT) morphology and BAT-associated gene expression compared to other adipose depots, including the interscapular BAT (iBAT). scBAT was as sensitive to cold induced thermogenesis as iBAT and showed reduced thermogenic effect under thermoneutrality. While both scBAT and iBAT are sensitive to cold, the expression of genes involved …

Health-Related Quality Of Life In Parents And Partners Of People With Type 1 Diabetes: Development And Validation Of Type 1 Diabetes And Life (T1dal) Measures, Marisa E Hilliard, Charles G Minard, David G Marrero, Maartje De Wit, Stephanie N Dubose, Alandra Verdejo, Sarah S Jaser, Davida Kruger, Roshanak Monzavi, Viral N Shah, R Paul Wadwa, Ruth S Weinstock, Debbe Thompson, Viena T Cao, Barbara J Anderson

Children’s Nutrition Research Center Staff Publications

Introduction: Despite the significant impact of type 1 diabetes (T1D) on family, few instruments are available to assess health-related quality of life (HRQOL) among family members of people with T1D. This study aimed to develop and evaluate the psychometric properties of new measures of diabetes-specific HRQOL for parents and partners of people with T1D. We report on the multistep development and validation process for the self-report Type 1 Diabetes and Life (T1DAL) measures, with versions for parents of youth age <8, 8-11, 12-17, and 18-25 years, and for partners of people age ≥18 years with T1D.

Method: First, we conducted qualitative interviews (total parents/partners n = 38) to develop draft measures and piloted them (total n …

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 …

Perceptions Of Family-Level Social Factors That Influence Health Behaviors In Latinx Adolescents And Young Adults At High Risk For Type 2 Diabetes, Erica G Soltero, Neeku Navabi, Felipe G Castro, Stephanie L Ayers, Jenny Mendez, Deborah I Thompson, Gabriel Q Shaibi

Children’s Nutrition Research Center Staff Publications

Given that health behaviors occur within the context of familial social relationships, a deeper understanding of social factors that influence health behaviors in Latinx families is needed to develop more effective diabetes prevention programming. This qualitative study identified perceived family-level social factors that influence health behaviors in Latinx adolescents (12–16 years; N = 16) and young adults (18–24 years; N = 15) with obesity and explored differences in perceptions across sex and age. Participants completed an in-depth interview that was recorded, transcribed, and coded using thematic content analysis. Emergent themes central to health behaviors included: perceived parental roles and responsibilities, …

A Neural Basis For Brain Leptin Action On Reducing Type 1 Diabetic Hyperglycemia, Shengjie Fan, Yuanzhong Xu, Yungang Lu, Zhiying Jiang, Hongli Li, Jessie C Morrill, Jing Cai, Qi Wu, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Cheng Huang, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

Central leptin action rescues type 1 diabetic (T1D) hyperglycemia; however, the underlying mechanism and the identity of mediating neurons remain elusive. Here, we show that leptin receptor (LepR)-expressing neurons in arcuate (LepRArc) are selectively activated in T1D. Activation of LepRArc neurons, Arc GABAergic (GABAArc) neurons, or arcuate AgRP neurons, is able to reverse the leptin’s rescuing effect. Conversely, inhibition of GABAArc neurons, but not AgRP neurons, produces leptin-mimicking rescuing effects. Further, AgRP neuron function is not required for T1D hyperglycemia or leptin’s rescuing effects. Finally, T1D LepRArc neurons show defective nutrient sensing and signs of cellular energy deprivation, which are …

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 = …

Identifying And Predicting Food Parenting Practice Profiles Among Canadian Parents, Claire N Tugault-Lafleur, Olivia De-Jongh González, Teresia M O'Connor, Sheryl O Hughes, Louise C Mâsse

Children’s Nutrition Research Center Staff Publications

Background: Food parenting practices (FPP) can affect children's eating behaviours, yet little is known about how various FPP co-occur. The primary aim was to identify profiles of FPPs use among Canadian parents. Secondary aims included examining sociodemographic correlates of FPP profiles and evaluating whether children's eating behaviours differed across FPP profiles.

Methods: Parents (n = 799) of 5-12-year-old children completed a validated FPP Item Bank and the Children's Eating Behaviour Questionnaire. Latent Class Analysis (LCA) was used to identify distinct FPP profiles. Regression analyses were used to explore associations between FPP profiles, sociodemographic variables (race, sex and education) and children's …

N-3 Fatty Acid Biomarkers And Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project Of 20 Prospective Cohort Studies, Frank Qian, Andres V Ardisson Korat, Fumiaki Imamura, Matti Marklund, Nathan Tintle, Jyrki K Virtanen, Xia Zhou, Julie K Bassett, Heidi Lai, Yoichiro Hirakawa, Kuo-Liong Chien, Alexis C Wood, Maria Lankinen, Rachel A Murphy, Cecilia Samieri, Kamalita Pertiwi, Vanessa D De Mello, Weihua Guan, Nita G Forouhi, Nick Wareham, Interact Consortium Frank B Hu, Ulf Riserus, Lars Lind, William S Harris, Aladdin H Shadyab, Jennifer G Robinson, Lyn M Steffen, Allison Hodge, Graham G Giles, Toshiharu Ninomiya, Matti Uusitupa, Jaakko Tuomilehto, Jaana Lindström, Markku Laakso, David S Siscovick, Catherine Helmer, Johanna M Geleijnse, Jason H Y Wu, Amanda Fretts, Rozenn N Lemaitre, Renata Micha, Dariush Mozaffarian, Qi Sun

Children’s Nutrition Research Center Staff Publications

Objective: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

Research design and methods: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed …

A Hindbrain Dopaminergic Neural Circuit Prevents Weight Gain By Reinforcing Food Satiation, Yong Han, Guobin Xia, Yanlin He, Yang He, Monica Farias, Yong Xu, Qi Wu

Children’s Nutrition Research Center Staff Publications

The neural circuitry mechanism that underlies dopaminergic (DA) control of innate feeding behavior is largely uncharacterized. Here, we identified a subpopulation of DA neurons situated in the caudal ventral tegmental area (cVTA) directly innervating DRD1-expressing neurons within the lateral parabrachial nucleus (LPBN). This neural circuit potently suppresses food intake via enhanced satiation response. Notably, this cohort of DAcVTA neurons is activated immediately before the cessation of each feeding bout. Acute inhibition of these DA neurons before bout termination substantially suppresses satiety and prolongs the consummatory feeding. Activation of postsynaptic DRD1LPBN neurons inhibits feeding, whereas genetic deletion of Drd1 within the …

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.

Sirt3 Is Required For Liver Regeneration But Not For The Beneficial Effect Of Nicotinamide Riboside, Sarmistha Mukherjee, James Mo, Lauren M Paolella, Caroline E Perry, Jade Toth, Mindy M Hugo, Qingwei Chu, Qiang Tong, Karthikeyani Chellappa, Joseph A Baur

Children’s Nutrition Research Center Staff Publications

Liver regeneration is critical to survival after traumatic injuries, exposure to hepatotoxins, or surgical interventions, yet the underlying signaling and metabolic pathways remain unclear. In this study, we show that hepatocyte-specific loss of the mitochondrial deacetylase SIRT3 drastically impairs regeneration and worsens mitochondrial function after partial hepatectomy. Sirtuins, including SIRT3, require NAD as a cosubstrate. We previously showed that the NAD precursor nicotinamide riboside (NR) promotes liver regeneration, but whether this involves sirtuins has not been tested. Here, we show that despite their NAD dependence and critical roles in regeneration, neither SIRT3 nor its nuclear counterpart SIRT1 is required for …

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, …

An Arabidopsis Oxalyl-Coa Decarboxylase, Atoxc, Is Important For Oxalate Catabolism In Plants, Justin Foster, Ninghui Cheng, Vincent Paris, Lingfei Wang, Jin Wang, Xiaoqiang Wang, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

Considering the widespread occurrence of oxalate in nature and its broad impact on a host of organisms, it is surprising that so little is known about the turnover of this important acid. In plants, oxalate oxidase is the most well-studied enzyme capable of degrading oxalate, but not all plants possess this activity. Recently, acyl-activating enzyme 3 (AAE3), encoding an oxalyl-CoA synthetase, was identified in Arabidopsis. This enzyme has been proposed to catalyze the first step in an alternative pathway of oxalate degradation. Since this initial discovery, this enzyme and proposed pathway have been found to be important to other plants …

Stakeholder Perspectives And Sustainability Of An Integrated Care Model For The Prevention And Management Of Obesity: The Childhood Obesity Research Demonstration (Cord) Project, Rebecca E Lee, Nathan H Parker, Allen M Hallett, Dennis Kao, Maria J Modelska, Hanadi S Rifai, Erica G Soltero, Daniel P O'Connor

Children’s Nutrition Research Center Staff Publications

Although reliable strategies exist to promote healthy habits that reduce childhood obesity, the sustainability of these strategies remains an ongoing public health challenge. This study aimed to identify factors experienced in a large, multisite project aimed at reducing childhood obesity that might contribute to project sustainability. Hypothesized constructs underpinning sustainability included replicability, continuation of benefits, institutionalization, and community capacity. Key informants (n = 27) completed 60 min, in-depth interviews, which were audio recorded and transcribed. Transcripts were first coded using a combined deductive and inductive approach. Four major themes emerged (with numerous subthemes): developing partnerships, challenges to the sustainability …

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), …

A Standard Calculation Methodology For Human Doubly Labeled Water Studies, John R Speakman, Yosuke Yamada, Hiroyuki Sagayama, Elena S F Berman, 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 J A Camps, Graeme L Close, Jamie A Cooper, Seth A Creasy, Sai Krupa Das, Richard Cooper, Lara R Dugas, Cara B Ebbeling, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije 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, David S Ludwig, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa 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 U Loechl, Edward L Melanson, Amy H Luke, Herman Pontzer, Jennifer Rood, Dale A Schoeller, Klaas R Westerterp, William W Wong

Children’s Nutrition Research Center Staff Publications

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.

Genetic Variants And Physical Activity Interact To Affect Bone Density In Hispanic Children, Ruixue Hou, Shelley A Cole, Mariaelisa Graff, Yujie Wang, Karin Haack, Sandra Laston, Nitesh R Mehta, Roman J Shypailo, Margaret L Gourlay, Anthony G Comuzzie, Kari E North, Nancy F Butte, Venkata Saroja Voruganti

Children’s Nutrition Research Center Staff Publications

Background: Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study.

Methods: Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine …

Rationale And Design Of The Baylor Infant Twin Study-A Study Assessing Obesity-Related Risk Factors From Infancy, Shabnam R Momin, Mackenzie K Senn, Scott Buckley, Neil R M Buist, Manisha Gandhi, Amy B Hair, Sheryl O Hughes, Kelly R Hodges, William C Lange, Maria A Papaioannou, Mimi Phan, Robert A Waterland, Alexis C Wood

Children’s Nutrition Research Center Staff Publications

Background: Early childhood (0-3 years) is a critical period for obesity prevention, when tendencies in eating behaviors and physical activity are established. Yet, little is understood about how the environment shapes children's genetic predisposition for these behaviors during this time. The Baylor Infant Twin Study (BITS) is a two phase study, initiated to study obesity risk factors from infancy. Data collection has been completed for Phase 1 in which three sub-studies pilot central measures for Phase 2. A novel infant temperament assessment, based on observations made by trained researchers was piloted in Behavior Observation Pilot Protocol (BOPP) study, a new …

Overview Of Breath Testing In Clinical Practice In North America, Buford L Nichols, Robert D Baker, Susan S Baker

Children’s Nutrition Research Center Staff Publications

Human breath is an easily, noninvasively obtained substance. It offers insight into metabolism and is used to diagnose disaccharide malabsorption, infection, small bowel bacterial over growth, and transit times. Herein, we discuss the readily available clinical breath tests, how they function, how they are administered and interpreted and some pitfalls in their use.

Fructan-Sensitive Children With Irritable Bowel Syndrome Have Distinct Gut Microbiome Signatures, Bruno P Chumpitazi, Kristi L Hoffman, Daniel P Smith, Ann R Mcmeans, Salma Musaad, James Versalovic, Joseph F Petrosino, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Background: Dietary fructans may worsen gastrointestinal symptoms in children with irritable bowel syndrome (IBS).

Aim: To determine whether gut microbiome composition and function are associated with childhood IBS fructan-induced symptoms.

Methods: Faecal samples were collected from 38 children aged 7-17 years with paediatric Rome III IBS, who previously completied a double-blind, randomised, placebo-controlled crossover (fructan vs maltodextrin) trial. Fructan sensitivity was defined as an increase of ≥30% in abdominal pain frequency during the fructan diet. Gut microbial composition was determined via 16Sv4 rDNA sequencing. LEfSe evaluated taxonomic composition differences. Tax4Fun2 predicted microbial fructan metabolic pathways.

Results: At baseline, 17 fructan-sensitive …

Parenteral Lipid Emulsions Induce Unique Ileal Fatty Acid And Metabolomic Profiles But Do Not Increase The Risk Of Necrotizing Enterocolitis In Preterm Pigs, William Yakah, Pratibha Singh, Joanne Brown, Barbara Stoll, Doug Burrin, Muralidhar H Premkumar, Hasan H Otu, Xuesong Gu, Simon T Dillon, Towia A Libermann, Steven D Freedman, Camilia R Martin

Children’s Nutrition Research Center Staff Publications

Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. Forty-two preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood …

Parenteral Fish-Oil Containing Lipid Emulsions Limit Initial Lipopolysaccharide-Induced Host Immune Responses In Preterm Pigs, William Yakah, David Ramiro-Cortijo, Pratibha Singh, Joanne Brown, Barbara Stoll, Madhulika Kulkarni, Berthe C Oosterloo, Doug Burrin, Krishna Rao Maddipati, Raina N Fichorova, Steven D Freedman, Camilia R Martin

Children’s Nutrition Research Center Staff Publications

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS—lyophilized Escherichia coli) or saline. Plasma was collected for …

Agrp Neurons Trigger Long-Term Potentiation And Facilitate Food Seeking, Chunmei Wang, Wenjun Zhou, Yang He, Tiffany Yang, Pingwen Xu, Yongjie Yang, Xing Cai, Julia Wang, Hesong Liu, Meng Yu, Chen Liang, Tingting Yang, Hailan Liu, Makoto Fukuda, Qingchun Tong, Qi Wu, Zheng Sun, Yanlin He, Yong Xu

Children’s Nutrition Research Center Staff Publications

Sufficient feeding is essential for animals' survival, which requires a cognitive capability to facilitate food seeking, but the neurobiological processes regulating food seeking are not fully understood. Here we show that stimulation of agouti-related peptide-expressing (AgRP) neurons triggers a long-term depression (LTD) of spontaneous excitatory post-synaptic current (sEPSC) in adjacent pro-opiomelanocortin (POMC) neurons and in most of their distant synaptic targets, including neurons in the paraventricular nucleus of the thalamus (PVT). The AgRP-induced sEPCS LTD can be enhanced by fasting but blunted by satiety signals, e.g. leptin and insulin. Mice subjected to food-seeking tasks develop similar neural plasticity in AgRP-innervated …