Digital Commons Network^™

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 …

Breast Cancer Risk For Female Relatives Of Male Breast Cancer Patients With Negative Brca1/2 Testing, Emily Martin

Dissertations and Theses (Open Access)

Risk models exist to estimate a female’s lifetime risk of breast cancer in the absence of a hereditary predisposition to cancer, namely Hereditary Breast and Ovarian Cancer syndrome. These risk models consider various factors such as reproductive history and family history, but few models take a family history of male breast cancer into account. This study aims to evaluate if prevalence of breast cancer among female relatives is higher when there is a family history of male breast cancer in the context of uninformative BRCA1 and BRCA2 testing. This information may aid in the process of risk assessments for patients …

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 …

Endogenous Mechanisms Regulating Myeloid Cell Mediated Inflammation During Acute Lung Injuries, Nathaniel Berg

Dissertations and Theses (Open Access)

Acute lung injuries (ALI) can result from both direct insults (e.g. pneumonia or inhalation injury), or systemic conditions such as sepsis or trauma. Current treatment options for patients are limited to supportive care and novel approaches are urgently needed. Appreciating the role of excessive inflammation that underlies the pathophysiology of ALI, we sought to identify endogenous mechanisms that dampen inflammation. Here we investigated two pathways that worked to limit excessive pulmonary inflammation in myeloid cells using a mouse model of sepsis-associated ALI. In the first approach we screened for microRNAs during the recovery phase of ALI that could potentially regulate …

Unraveling Host-Gut Microbiota Dialogue And Its Impact On Response To Immune Checkpoint Blockade, Alexandria Cogdill

Dissertations and Theses (Open Access)

Cancer is a disease with only one degree of separation, affecting one in two men and one in three women in their lifetimes; accounting for 1 of every 6 deaths. While cancer mortality rates continue to improve, incidence rates are expected to rise and shift through 2050 due to epidemiological and demographic transitions worldwide. As such, it is imperative to continue to investigate and improve our understanding of both disease etiology and hallmarks of response to treatment. Currently, conventional therapies include, but are not limited to, surgery, chemotherapy, and radiotherapy. However, within the past decade, major advances have been made …

Investigating Barriers Experienced By Underrepresented Minorities In Becoming A Competitive Genetic Counseling Applicant, Katie Huang

Dissertations and Theses (Open Access)

Representation for both racial/ethnic and gender identity minorities in genetic counseling (GC) remains the lowest among similar healthcare professions. Barriers that underrepresented minority (URM) individuals face in becoming a competitive GC applicant have not yet been described. Academic capital (AC) is a theoretical framework describing the social processes necessary for individuals to navigate and succeed in higher education. This study aimed to characterize barriers experienced by applicants who self-identify as underrepresented and to explore how AC could identify areas for intervention. Prospective GC applicants for the 2021/2022 cycles were recruited to complete an anonymous online survey in Qualtrics through a …

Amino Acid Metabolism And Autophagy In Skeletal Development And Homeostasis, Akiko Suzuki, Junichi Iwata

Faculty, Staff and Student Publications

Bone is an active organ that is continuously remodeled throughout life via formation and resorption; therefore, a fine-tuned bone (re)modeling is crucial for bone homeostasis and is closely connected with energy metabolism. Amino acids are essential for various cellular functions as well as an energy source, and their synthesis and catabolism (e.g., metabolism of carbohydrates and fatty acids) are regulated through numerous enzymatic cascades. In addition, the intracellular levels of amino acids are maintained by autophagy, a cellular recycling system for proteins and organelles; under nutrient deprivation conditions, autophagy is strongly induced to compensate for cellular demands and to restore …

Type 2 Diabetes Subgroups, Risk For Complications, And Differential Effects Due To An Intensive Lifestyle Intervention, Michael P Bancks, Haiying Chen, Ashok Balasubramanyam, Alain G Bertoni, Mark A Espeland, Steven E Kahn, Scott Pilla, Elizabeth Vaughan, Lynne E Wagenknecht

Faculty, Staff and Students Publications

OBJECTIVE: We reevaluated the Action for Health in Diabetes (Look AHEAD) intervention, incorporating diabetes subgroups, to identify whether intensive lifestyle intervention (ILI) is associated with differential risk for cardiovascular disease (CVD) by diabetes subgroup.

RESEARCH DESIGN AND METHODS: In the Look AHEAD trial, 5,145 participants, aged 45-76 years, with type 2 diabetes (T2D) and overweight or obesity were randomly assigned to 10 years of ILI or a control condition of diabetes support and education. The ILI focused on weight loss through decreased caloric intake and increased physical activity. To characterize diabetes subgroups, we applied k-means clustering to data on age …

Acetyl-Coa And Metabolite Fluxes Regulate White Adipose Tissue Expansion, Jessica B Felix, Aaron R Cox, Sean M Hartig

Faculty, Staff and Students Publications

White adipose tissue (WAT) depends on coordinated regulation of transcriptional and metabolic pathways to respond to whole-body energy demands. We highlight metabolites that contribute to biosynthetic reactions for WAT expansion. Recent studies have precisely defined how byproducts of carbohydrate and lipid metabolism affect physiological and endocrine functions in adipocytes. We emphasize the critical emerging roles of short-chain fatty acids (SCFAs) and tricarboxylic acid (TCA) cycle metabolites that connect lipogenesis to WAT energy balance and endocrine functions. These insights address how adipocytes use small molecules generated from central carbon metabolism to measure responses to nutritional stress.

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 …

Associations Of Abdominal Pain And Psychosocial Distress Measures With Health-Related Quality-Of-Life In Pediatric Healthy Controls And Irritable Bowel Syndrome, John M Hollier, Danita I Czyzewski, Mariella M Self, Yan Liu, Erica M Weidler, Miranda A L Van Tilburg, James W Varni, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: Children with irritable bowel syndrome (IBS) have lower health-related quality-of-life (HRQOL) than healthy controls (HC). Abdominal pain and psychosocial distress are negatively associated with HRQOL, although their relative effect is unclear.

AIM: The aim of this study was to compare the relative associations of abdominal pain and psychosocial distress with HRQOL in HC and IBS.

STUDY: Baseline abdominal pain, psychosocial distress, and HRQOL measures were obtained from HC and IBS pediatric clinical trial participants. Regression assessed which measures were most strongly associated with Physical and Psychosocial HRQOL separately by group. Interaction analyses examined group differences in the associations of …

Restructuring The Gut Microbiota By Intermittent Fasting Lowers Blood Pressure, Huanan Shi, Bojun Zhang, Taylor Abo-Hamzy, James W Nelson, Chandra Shekar R Ambati, Joseph F Petrosino, Robert M Bryan, David J Durgan

Faculty, Staff and Students Publications

Rationale:

In recent years, it has been demonstrated that a pathological change in the gut microbiota, termed gut dysbiosis, can be an underlying factor for the development of hypertension. Prevention of this dysbiosis can attenuate or abolish hypertension. Translational mechanisms to prevent gut dysbiosis as well as understanding of the mechanisms linking gut dysbiosis to hypertension are lacking.

Objective:

We first examined the efficacy of intermittent fasting (IF) in altering the gut microbiota and lowering blood pressure (BP). Next, we utilized a multi-omics approach to examine microbial influenced metabolites that may serve as the link between the gut microbiota and …

Proteomic Investigation Of Glyceraldehyde-Derived Intracellular Ages And Their Potential Influence On Pancreatic Ductal Cells, Lakmini Senavirathna, Cheng Ma, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

Glyceraldehyde-derived advanced glycation end products (AGEs) play an important role in the pathogenesis of many diseases including cancer. Accumulation of intracellular AGEs could stimulate cancer induction and facilitate cancer progression. We evaluated the toxic effect of glyceraldehyde-derived intracellular AGEs on normal and malignant pancreatic ductal cells by assessing the cell viability, toxicity, and oxidative stress, followed by proteomic analysis. Our functional studies showed that pancreatic cancer cells (PANC-1 and MIA PaCa-2) were more resistant to glyceraldehyde treatment compared to normal pancreatic ductal epithelial cells (HPDE), while cytotoxicity effects were observed in all cell types. Furthermore, using 13C isotopic labeled glyceraldehyde, …

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.

Functional Interpretation Of Atad3a Variants In Neuro-Mitochondrial Phenotypes, Zheng Yie Yap, Yo Han Park, Saskia B Wortmann, Adam C Gunning, Shlomit Ezer, Sukyeong Lee, Lita Duraine, Ekkehard Wilichowski, Kate Wilson, Johannes A Mayr, Matias Wagner, Hong Li, Usha Kini, Emily Davis Black, Kristin G Monaghan, James R Lupski, Sian Ellard, Dominik S Westphal, Tamar Harel, Wan Hee Yoon

Faculty, Staff and Students Publications

BACKGROUND: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

METHODS: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes. A Drosophila Atad3a Gal4 …

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, …

Rev-Erb In Gabaergic Neurons Controls Diurnal Hepatic Insulin Sensitivity, Guolian Ding, Xin Li, Xinguo Hou, Wenjun Zhou, Yingyun Gong, Fuqiang Liu, Yanlin He, Jia Song, Jing Wang, Paul Basil, Wenbo Li, Sichong Qian, Pradip Saha, Jinbang Wang, Chen Cui, Tingting Yang, Kexin Zou, Younghun Han, Christopher I Amos, Yong Xu, Li Chen, Zheng Sun

Faculty, Staff and Students Publications

Systemic insulin sensitivity shows diurnal rhythm with a peak at wakening1,2. The molecular mechanism underlying such a temporal pattern is unclear. Here we demonstrate that nuclear receptors Rev-erbα/β in the GABAergic neurons in the suprachiasmatic nucleus (SCNGABA) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviors under the regular light-dark cycles. Rev-erb regulates the rhythmic expression of genes involved in neurotransmission in the SCN and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at wakening causes glucose intolerance, while restoration …

Serial Block-Face Scanning Electron Microscopy (Sbf-Sem) Of Biological Tissue Samples, Justin A Courson, Paul T Landry, Thao Do, Eric Spehlmann, Pascal J Lafontant, Nimesh Patel, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

Serial block-face scanning electron microscopy (SBF-SEM) allows for the collection of hundreds to thousands of serially-registered ultrastructural images, offering an unprecedented three-dimensional view of tissue microanatomy. While SBF-SEM has seen an exponential increase in use in recent years, technical aspects such as proper tissue preparation and imaging parameters are paramount for the success of this imaging modality. This imaging system benefits from the automated nature of the device, allowing one to leave the microscope unattended during the imaging process, with the automated collection of hundreds of images possible in a single day. However, without appropriate tissue preparation cellular ultrastructure can …

Loss Of Bone Morphogenetic Protein-Binding Endothelial Regulator Causes Insulin Resistance, Hua Mao, Luge Li, Qiying Fan, Aude Angelini, Pradip K Saha, Huaizhu Wu, Christie M Ballantyne, Sean M Hartig, Liang Xie, Xinchun Pi

Faculty, Staff and Students Publications

Accumulating evidence suggests that chronic inflammation of metabolic tissues plays a causal role in obesity-induced insulin resistance. Yet, how specific endothelial factors impact metabolic tissues remains undefined. Bone morphogenetic protein (BMP)–binding endothelial regulator (BMPER) adapts endothelial cells to inflammatory stress in diverse organ microenvironments. Here, we demonstrate that BMPER is a driver of insulin sensitivity. Both global and endothelial cell-specific inducible knockout of BMPER cause hyperinsulinemia, glucose intolerance and insulin resistance without increasing inflammation in metabolic tissues in mice. BMPER can directly activate insulin signaling, which requires its internalization and interaction with Niemann-Pick C1 (NPC1), an integral membrane protein that …

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 …

Glucagon Blockade Restores Functional Β-Cell Mass In Type 1 Diabetic Mice And Enhances Function Of Human Islets, May-Yun Wang, E Danielle Dean, Ezekiel Quittner-Strom, Yi Zhu, Kamrul H Chowdhury, Zhuzhen Zhang, Shangang Zhao, Na Li, Reshing Ye, Young Lee, Yiyi Zhang, Shiuhwei Chen, Xinxin Yu, Derek C Leonard, Greg Poffenberger, Alison Von Deylen, S Kay Mccorkle, Amnon Schlegel, Kyle W Sloop, Alexander M Efanov, Ruth E Gimeno, Philipp E Scherer, Alvin C Powers, Roger H Unger, William L Holland

Faculty, Staff and Students Publications

We evaluated the potential for a monoclonal antibody antagonist of the glucagon receptor (Ab-4) to maintain glucose homeostasis in type 1 diabetic rodents. We noted durable and sustained improvements in glycemia which persist long after treatment withdrawal. Ab-4 promoted β-cell survival and enhanced the recovery of insulin+ islet mass with concomitant increases in circulating insulin and C peptide. In PANIC-ATTAC mice, an inducible model of β-cell apoptosis which allows for robust assessment of β-cell regeneration following caspase-8–induced diabetes, Ab-4 drove a 6.7-fold increase in β-cell mass. Lineage tracing suggests that this restoration of functional insulin-producing cells was at least partially …

Pegylated Arginine Deiminase Depletes Plasma Arginine But Maintains Tissue Arginine Availability In Young Pigs, Mahmoud A Mohammad, Inka C Didelija, Barbara Stoll, Trung C Nguyen, Juan C Marini

Faculty, Staff and Students Publications

Pegylated arginine deiminase (ADI-PEG20) results in the depletion of arginine with the production of isomolar amounts of citrulline. This citrulline has the potential to be utilized by the citrulline recycling pathway regenerating arginine and sustaining tissue arginine availability. The goal of this research was to test the hypothesis that ADI-PEG20 depletes circulating arginine in pigs but maintains tissue arginine concentration and function, and to characterize the kinetics of citrulline and arginine. Two multitracer approaches (bolus dose and primed-continuous infusion) were used to investigate the metabolism of arginine and citrulline in Control (

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 …

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 …

The Association Between Overnight Fasting And Body Mass Index In Older Adults: The Interaction Between Duration And Timing, Qian Xiao, Cici Bauer, Tracy Layne, Mary Playdon

Faculty, Staff and Student Publications

BACKGROUND: Circadian rhythms play an important role in the regulation of eating and fasting, and mistimed dietary intakes may be detrimental to metabolic health. Extended overnight fasting has been proposed as a strategy to better align the eating-fasting cycle with the internal circadian clock, and both observational and experimental studies have linked longer overnight fasting with lower body weight. However, it remains unclear if the timing of overnight fasting modifies the relationship between fasting duration and weight outcomes.

METHODS: The current study included 495 men and 499 women age 50-74 years. Dietary intake over 12 months was assessed by 24-h …

In Vivo Transplantation Of Human Intestinal Organoids Enhances Select Tight Junction Gene Expression, Mariaelena A Boyle, David J Sequeira, Eoin P Mcneill, Zachary K Criss, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

BACKGROUND: Short bowel syndrome is a potentially fatal condition with inadequate management options. Tissue-engineered small intestine (TESI) is a promising solution, but confirmation of TESI function will be crucial before human application. We sought to define intestinal epithelial barrier function in human intestinal organoid (HIO)-derived TESI.

MATERIALS AND METHODS: HIOs were generated in vitro from human embryonic stem cells. After 1 mo, HIOs were collected for analysis or transplanted into the kidney capsule of immunocompromised mice. Transplanted HIOs (tHIOs) were harvested for analysis at 4 or 8 wk. Reverse transcription quantitative polymerase chain reaction and immunofluorescent staining were performed for …