Endocrinology, Diabetes, and Metabolism Commons^™

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 …

Deficiency Of Stat1 In Cd11c+ Cells Alters Adipose Tissue Inflammation And Improves Metabolic Dysfunctions In Mice Fed A High-Fat Diet, Antu Antony, Zeqin Lian, Xiaoyuan Dai Perrard, Jerry Perrard, Hua Liu, Aaron R Cox, Pradip Saha, Lothar Hennighausen, Sean M Hartig, Christie M Ballantyne, Huaizhu Wu

Faculty, Staff and Students Publications

CD11c+ macrophages/dendritic cells (MDCs) are increased and display the classically activated M1-like phenotype in obese adipose tissue (AT) and may contribute to AT inflammation and insulin resistance. Stat1 is a key transcription factor for MDC polarization into the M1-like phenotype. Here, we examined the role of Stat1 in obesity-induced AT MDC polarization and inflammation and insulin resistance using mice with specific knockout of Stat1 in MDCs (cKO). Stat1 was upregulated and phosphorylated, indicating activation, early and persistently in AT and AT MDCs of wild-type mice fed a high-fat diet (HFD). Compared with littermate controls, cKO mice fed an HFD (16 …

Testosterone Therapy And Bone Quality In Men With Diabetes And Hypogonadism: Study Design And Protocol, Vittoria Russo, Georgia Colleluori, Rui Chen, Sanjay Mediwala, Clifford Qualls, Michael Liebschner, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

CONTEXT: Type 2 diabetes mellitus (T2D) is often accompanied by male hypogonadism and both conditions are associated with increased risk for fractures. Testosterone (T) has been shown to improve the bone health of hypogonadal men but has not been tested in patients who also have T2D in addition to low T. To date, there is no treatment that is specifically recommended for bone disease among patients with T2D. This study will evaluate the effect of T therapy on the bone health of male veterans with low T who also have T2D.

METHODS: This is a randomized double-blind placebo-controlled trial of …

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 …

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 …

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 …

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.

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 …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Intestinal Stem Cell-Derived Enteroids From Morbidly Obese Patients Preserve Obesity-Related Phenotypes: Elevated Glucose Absorption And Gluconeogenesis, Nesrin M Hasan, Kelli F Johnson, Jianyi Yin, Nicholas W Baetz, Lea Fayad, Vadim Sherman, Sarah E Blutt, Mary K Estes, Vivek Kumbhari, Nicholas C Zachos, Olga Kovbasnjuk

Faculty, Staff and Students Publications

OBJECTIVE: The mechanisms behind the efficacy of bariatric surgery (BS) for treating obesity and type 2 diabetes, particularly with respect to the influence of the small bowel, remain poorly understood. In vitro and animal models are suboptimal with respect to their ability to replicate the human intestinal epithelium under conditions induced by obesity. Human enteroids have the potential to accelerate the development of less invasive anti-obesity therapeutics if they can recapitulate the pathophysiology of obesity. Our aim was to determine whether adult stem cell-derived enteroids preserve obesity-characteristic patient-specific abnormalities in carbohydrate absorption and metabolism.

METHODS: We established 24 enteroid lines …

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 …

Probiotic Vsl#3 Treatment Reduces Colonic Permeability And Abdominal Pain Symptoms In Patients With Irritable Bowel Syndrome, Prapaporn Boonma, Jordan M Shapiro, Emily B Hollister, Shyam Badu, Qinglong Wu, Erica M Weidler, Bincy P Abraham, Sridevi Devaraj, Ruth Ann Luna, James Versalovic, Margaret M Heitkemper, Tor C Savidge, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Background: Little is known regarding the clinical impact of treatment and treatment duration of probiotic VSL#3 on gut and microbiome function in irritable bowel syndrome (IBS). As part of a safety trial, we assessed the effect of VSL#3 treatment duration on abdominal pain, stooling, gut permeability, microbiome composition and function.

Methods: Adults with IBS were randomized into an open label trial to receive the probiotic VSL#3 for 4 or 8 weeks. Adverse events, abdominal pain, and stooling patterns were recorded daily. Gut permeability, fecal bile acid levels, and microbiome composition were profiled at baseline and after treatment.

Results: Fifteen subjects …

On The Joint Role Of Non-Hispanic Black Race/Ethnicity And Weight Status In Predicting Postmenopausal Weight Gain, Christopher N Ford, Shine Chang, Alexis C Wood, Joann E Manson, David O Garcia, Helena Laroche, Chloe E Bird, Mara Z Vitolins

Children’s Nutrition Research Center Staff Publications

Objectives: To determine how baseline weight status contributes to differences in postmenopausal weight gain among non-Hispanic Blacks (NHBs) and non-Hispanic Whites (NHWs).

Methods: Data were included from 70,750 NHW and NHB postmenopausal women from the Women's Health Initiative Observational Study (WHI OS). Body Mass Index (BMI) at baseline was used to classify women as having normal weight, overweight, obese class I, obese class II or obese class III. Cox proportional hazards was used to estimate the hazard of a 10% or more increase in weight from baseline.

Results: In both crude and adjusted models, NHBs were more likely to experience …

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 …

Associations Between Independent Assessments Of Child Appetite Self-Regulation: A Narrative Review, Maria A Papaioannou, Nilda Micheli, Thomas G Power, Jennifer O Fisher, Sheryl O Hughes

Children’s Nutrition Research Center Staff Publications

A variety of eating behaviors among children have been associated with obesity risk and are thought to broadly reflect child appetite self-regulation (ASR). While ASR is thought to occur on cognitive, emotional, motivational, biological, and behavioral levels, the inter-relatedness of ASR constructs as assessed by different methods/measures is not well-characterized. This narrative review describes the correspondence between different methods/measures of child ASR constructs as assessed by self-report questionnaires and/or observational tasks and their relationship to child standardized body mass index (BMIz). Research involving at least two different methods/measures is presented including observational tasks such as the Eating in the Absence …

Crucial Role Of Mammalian Glutaredoxin 3 In Cardiac Energy Metabolism In Diet-Induced Obese Mice Revealed By Transcriptome Analysis, Ninghui Cheng, Qianxing Mo, Jimmonique Donelson, Lingfei Wang, Ghislain Breton, George G Rodney, Jin Wang, Kendal D Hirschi, Xander H T Wehrens, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

Obesity is often associated with metabolic dysregulation and oxidative stress with the latter serving as a possible unifying link between obesity and cardiovascular complications. Glutaredoxins (Grxs) comprise one of the major antioxidant systems in the heart. Although Grx3 has been shown to act as an endogenous negative regulator of cardiac hypertrophy and heart failure, its metabolic impact on cardiac function in diet-induced obese (DIO) mice remains largely unknown. In the present study, analysis of Grx3 expression indicated that Grx3 protein levels, but not mRNA levels, were significantly increased in the hearts of DIO mice. Cardiac-specific Grx3 deletion (Grx3 CKO) mice …

Wearable Activity Tracking Device Use In An Adolescent Weight Management Clinic: A Randomized Controlled Pilot Trial, Kanika Bowen-Jallow, Omar Nunez-Lopez, Alex Wright, Erika Fuchs, Mollie Ahn, Elizabeth Lyons, Daniel Jupiter, Lindsey Berry, Oscar Suman, Ravi S Radhakrishnan, Andrea M Glaser, Deborah I Thompson

Children’s Nutrition Research Center Staff Publications

Background: The use of physical activity tracker devices has increased within the general population. However, there is limited medical literature studying the efficacy of such devices in adolescents with obesity. In this study, we explored the feasibility of using wearable activity tracking devices as an adjunct intervention on adolescents with obesity.

Methods: Randomized controlled pilot trial evaluated the feasibility (attrition ≤50%) of an activity tracking intervention (ATI) and its effects on weight loss in adolescents with obesity enrolled in an adolescent weight management clinic (AWMC). Outcomes included feasibility (attrition rate) and absolute change in BMI. Differences between groups at 6, …

Food/Non-Food Classification Of Real-Life Egocentric Images In Low- And Middle-Income Countries Based On Image Tagging Features, Guangzong Chen, Wenyan Jia, Yifan Zhao, Zhi-Hong Mao, Benny Lo, Alex K Anderson, Gary Frost, Modou L Jobarteh, Megan A Mccrory, Edward Sazonov, Matilda Steiner-Asiedu, Richard S Ansong, Thomas Baranowski, Lora Burke, Mingui Sun

Children’s Nutrition Research Center Staff Publications

Malnutrition, including both undernutrition and obesity, is a significant problem in low- and middle-income countries (LMICs). In order to study malnutrition and develop effective intervention strategies, it is crucial to evaluate nutritional status in LMICs at the individual, household, and community levels. In a multinational research project supported by the Bill & Melinda Gates Foundation, we have been using a wearable technology to conduct objective dietary assessment in sub-Saharan Africa. Our assessment includes multiple diet-related activities in urban and rural families, including food sources (e.g., shopping, harvesting, and gathering), preservation/storage, preparation, cooking, and consumption (e.g., portion size and nutrition analysis). …

Associations Between Lipoprotein Subfractions And Area And Density Of Abdominal Muscle And Intermuscular Adipose Tissue: The Multi-Ethnic Study Of Atherosclerosis, Megan M Marron, Matthew Allison, Alka M Kanaya, Britta Larsen, Alexis C Wood, David Herrington, Philip Greenland, Iva Miljkovic

Children’s Nutrition Research Center Staff Publications

Skeletal muscle quantity and quality decrease with older age, which is partly attributed to ectopic fat infiltration and has negative metabolic consequences. To inform efforts to preserve skeletal muscle with aging, a better understanding of biologic correlates of quantity and quality of muscle and intermuscular adipose tissue (IMAT) is needed. We used targeted lipidomics of lipoprotein subfractions among 947 Multi-Ethnic Study of Atherosclerosis participants to provide a detailed metabolic characterization of area and density of abdominal muscle and IMAT. Serum lipoprotein subfractions were measured at the first visit using 1H-Nuclear Magnetic Resonance spectroscopy. Muscle and IMAT area (cm

A Computational Pipeline To Infer Alternative Poly-Adenylation From 3′ Sequencing Data, Hari Krishna Yalamanchili, Nathan D Elrod, Madeline K Jensen, Ping Ji, Ai Lin, Eric J Wagner, Zhandong Liu

Children’s Nutrition Research Center Staff Publications

An increasing number of investigations have established alternative polyadenylation (APA) as a key mechanism of gene regulation through altering the length of 3' untranslated region (UTR) and generating distinct mRNA termini. Further, appreciation for the significance of APA in disease contexts propelled the development of several 3' sequencing techniques. While these RNA sequencing technologies have advanced APA analysis, the intrinsic limitation of 3' read coverage and lack of appropriate computational tools constrain precise mapping and quantification of polyadenylation sites. Notably, Poly(A)-ClickSeq (PAC-seq) overcomes limiting factors such as poly(A) enrichment and 3' linker ligation steps using click-chemistry. Here we provide an …

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 …

Thyroid Storm In A Patient With Covid-19, Angela N Rao, Ruaa Y Al-Ward, Ruchi Gaba

Faculty, Staff and Students Publications

OBJECTIVE: A thyroid storm is a severe exacerbation of thyrotoxicosis that can cause significant morbidity and mortality. The emergence of the novel coronavirus (SARS-CoV-2) that originated in Wuhan, China, has become a worldwide pandemic. We present the first documented case of thyroid storm (as defined by the Burch-Wartofsky criteria) in a patient with COVID-19.

METHODS: Laboratory and diagnostic studies, including thyroid function tests, thyroid antibody testing, SARS-CoV-2 nasopharyngeal polymerase chain reaction testing, and thyroid ultrasound were performed.

RESULTS: A 25-year-old woman presented to the hospital with dry cough, dyspnea, palpitations, weight loss, diarrhea, and anxiety. Physical examination revealed exophthalmos with …

The E3 Ligase Traf4 Promotes Igf Signaling By Mediating Atypical Ubiquitination Of Irs-1, Wenjuan Yu, Ramesh Singh, Zhao Wang, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Insulin-like growth factor (IGF) is a potent mitogen that activates the IGF receptor (IGFR)/insulin receptor substrate (IRS) axis, thus stimulating growth in normal cells and uncontrolled cell proliferation in cancer. Posttranslational modifications of IRS such as ubiquitination tightly control IGF signaling, and we previously identified IRS-1 as a potential substrate for the E3 ubiquitin ligase TRAF4 using an unbiased screen. Here we provide evidence that TRAF4-mediated ubiquitination of IRS-1 is physiologically relevant and crucial for IGF signal transduction. Through site-directed mutagenesis we found that TRAF4 promotes an atypical K29-linked ubiquitination at the C-terminal end of IRS-1. Its depletion abolishes AKT …

Long Noncoding Rnas And Their Therapeutic Promise In Diabetic Nephropathy, Juan D Coellar, Jianyin Long, Farhad R Danesh

Faculty, Staff and Students Publications

Recent advances in large-scale RNA sequencing and genome-wide profiling projects have unraveled a heterogeneous group of RNAs, collectively known as long noncoding RNAs (lncRNAs), which play central roles in many diverse biological processes. Importantly, an association between aberrant expression of lncRNAs and diverse human pathologies has been reported, including in a variety of kidney diseases. These observations have raised the possibility that lncRNAs may represent unexploited potential therapeutic targets for kidney diseases. Several important questions regarding the functionality of lncRNAs and their impact in kidney diseases, however, remain to be carefully addressed. Here, we provide an overview of the main …