Medical Specialties Commons^™

The Overlooked Impact Of Background Diet And Adherence In Nutrition Trials, Javier I Ottaviani, Hagen Schroeter, Dennis M Bier, John W Erdman, Howard D Sesso, Joann E Manson, Gunter G C Kuhnle

Children’s Nutrition Research Center Staff Publications

Randomised controlled trials in nutrition (RCTN) face unique challenges, including the considerable influence of the background diet and the challenge of assuring intervention adherence by participants. The impact of these factors on the outcome of RCTNs has been difficult to quantify, but nutritional biomarkers represent a valuable tool to address these challenges. Using flavanols as a model dietary intervention and a set of recently validated flavanol biomarkers, we here investigated the impact of background diet and adherence on the outcomes of a subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS, NCT 02422745). We found that 20% of participants …

Src/Fn1 Pathway Activation Drives Tumor Cell Cluster Formation And Metastasis In Lung Cancer: A Promising Therapeutic Target, Zujun Que, Zhichao Xi, Dan Qi, Rongchen Dai, Yang Li, Mengfan Liu, Bin Luo, Jiajun Liu, Pan Yu, Yun Yang, Erxi Wu, Hongxi Xu, Jianhui Tian

Children’s Nutrition Research Center Staff Publications

Lung cancer remains the leading cause of cancer-related death globally, with metastasis driven by circulating tumor cells (CTCs)-particularly clusters-being a major treatment challenge. Despite their critical role, the biological differences between single CTCs and CTC clusters remain unclear. Here, we comprehensively compared their behavioral, transcriptomic, and proteomic profiles in lung cancer models. Compared with single cells, CTC clusters present enhanced metastatic potential, greater survival in the bloodstream and increased resistance to microenvironment. Mechanistically, the Src/FN1 pathway is centrally activated in clusters, promoting intercellular cohesion and protecting against immune clearance and stress in circulation. Pharmacological inhibition of Src with the clinical …

The Benefits Of Exercise Training In Combination With Weight Loss Therapies, Bryan C Jiang, Dennis T Villareal

Faculty, Staff and Students Publications

The primary treatment for obesity involves calorie restriction (CR) to promote dietary weight loss achieved through interventions including behavioral modification, bariatric surgery, and antiobesity medications. In adults with obesity, CR-induced weight loss enhances physical function and improves quality of life, while also reducing the burden of various obesity-related chronic conditions, including hypertension, diabetes, obstructive sleep apnea, and atherosclerotic heart disease. However, it is also associated with a decline in lean mass and bone mineral density, which increases the risk of sarcopenia and osteoporosis. When performed alongside CR, progressive resistance training (RT) attenuates this loss of lean mass and bone mass, …

Food Noise: Definition, Measurement, And Future Research Directions, Emily J Dhurandhar, Kevin C Maki, Nikhil V Dhurandhar, Theodore K Kyle, Sydney Yurkow, Misty A W Hawkins, Jon Agley, Emily H Ho, Lawrence J Cheskin, Thorkild I A Sørensen, Xi Rita Wang, David B Allison

Children’s Nutrition Research Center Staff Publications

The term food noise has been recently popularized by individuals managing their weight or adhering to specific diets for health reasons. Anecdotal evidence from patients and clinical observations suggests that food noise involves constant preoccupation with food-related decisions-such as which foods to eat, caloric intake, macronutrient balance, and meal timing-which can become intrusive and unpleasant. Food noise also appears to affect cognitive burden and quality of life, and is being cited as one reason weight-loss attempts fail. The increase in public discourse about food noise has highlighted its potential significance, yet a formal clinical definition and method of measurement of …

Risk Of Pancreatic Cancer In Glycemically Defined New-Onset Diabetes: A Prospective Cohort Study, Suresh T Chari, Bechien Wu, Camden Lopez, Eva Lustigova, Qiaoling Chen, Stephen K Van Den Eeden, Amethyst D Leimpeter, William Fisher, Amy Wood, Ashley S Alexander, John Valenta, Santhi Swaroop Vege, Erin E Carlson, Kari G Rabe, Phil A Hart, Lu Qian, Ying-Qi Zhao, Nadia Yosuf, Lynn Matrisian, Barbara Kenner, Jo Ann Rinaudo, Anirban Maitra, Ziding Feng

Faculty, Staff and Student Publications

Background & aims: The increased 3-year incidence of pancreatic cancer after new-onset diabetes observed in retrospective studies needs prospective validation. It is unknown whether incidence varies by race and ethnicity.

Methods: In a prospective, observational study using active real-time surveillance of electronic health records, we identified 18,838 adults 50 years or older with glycemically defined new-onset diabetes (GNOD). In this interim analysis, we report 3-year Kaplan-Meier estimates of the proportion diagnosed with pancreatic cancer after GNOD (absolute incidence [95% CI]) and associated standardized incidence ratio (SIR) by race and ethnicity, overall 3-year incidence of pancreatic cancer adjusting for racial distribution …

Human Extravillous Trophoblasts Require Src-2 For Sustained Viability, Migration, And Invasion, Vineet K Maurya, Pooja Popli, Bryan C Nikolai, David M Lonard, Ramakrishna Kommagani, Bert W O'Malley, John P Lydon

Faculty, Staff and Students Publications

Defective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execute their roles in placental development and function, while derailment of these cellular processes is linked to placental disorders. Although the cellular functions of extravillous trophoblasts are well recognized, our understanding of the pivotal molecular determinants of these functions is incomplete. Using the HTR-8/SVneo immortalized human extravillous trophoblast cell line, we report that steroid receptor coactivator-2 (SRC-2), a coregulator of transcription factor-mediated gene expression, is essential …

A Rare Case Of Familial Hypocalciuric Hypercalcemia In Patient With Pancreatitis, Muhammad Ijaz Khan, Tanvi Jain, Muhammad Mohsin Abid, Samra Israr, Muhammad Haris Khan

Journal of Community Hospital Internal Medicine Perspectives

Familial hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant condition caused by mutations in the calcium-sensing receptor gene (CASR), leading to asymptomatic hypercalcemia. Here, we report a case of hypercalcemia in a patient with acute pancreatitis, subsequently diagnosed with FHH. A 41-year-old male presented with abdominal pain and elevated pancreatic enzymes. Imaging revealed changes consistent with acute pancreatitis. Surprisingly, serum calcium was elevated, which is uncommon in acute pancreatitis. Further work-up demonstrated normal parathyroid hormone (PTH), PTH-related peptide (PTHrp), and vitamin D levels. A 24- hour urinary calcium excretion of 24 mg/24 hr and a calcium-to-creatinine clearance ratio (CCCR) of …

Artificial Intelligence For Detecting Non-Alcoholic Steatohepatitis (Nash), Muhammad Wildan Gifari, Yogi Ramadhani, Dhadhang Wahyu Kurniawan

Pharmaceutical Sciences and Research

Non-alcoholic steatohepatitis (NASH), an inflammatory disease of the liver, has recently raised concern among healthcare professionals worldwide due to its asymptomatic features, making early diagnosis challenging. If left unnoticed, NASH often progresses to lethal diseases such as liver fibrosis or hepatocellular carcinoma. Recent developments in the field of artificial intelligence (AI) might facilitate the early diagnosis of NASH in a more efficient manner, forming a promising strategy to diagnose patients. In simple terms, AI is any machine that is capable of human-level intelligence, including visual perception, speech recognition, or decision making. A subclass of AI, which particularly deals with knowledge-based …

Familial Hypocalciuric Hypercalcemia Across Three Generations: Exploring Coexistent Primary Hyperparathyroidism, Liada Itzel Guerrero Arroyo Md, Anda Raluca Gonciuela Md, Sachin Majumdar Md

Posters

FHH due to CASR R220W variant may present with phenotypic variability, including features classically associated with PHPT. Genetic testing is essential in ambiguous cases to avoid unnecessary surgical interventions.

Subclinical Hyperthyroidism Presenting As Urinary Frequency And Polyuria: A Case Report., Hameed H Salah, Elizabeth M Pines

Ambulatory and Primary Care Articles

Hyperthyroidism may present with a variety of symptoms including urinary frequency. This report discusses a case of subclinical hyperthyroidism presenting as generalized weakness, urinary frequency, polyuria, and intermittent diarrhea. However, this elderly patient had a complex past medical history including multinodular nontoxic thyroid goiter with tracheal deviation and multiple recent admissions for aspiration pneumonia, making the diagnosis of subclinical hyperthyroidism less obvious. The patient was managed with intravenous fluids and discharged on propranolol with recommendations to follow-up with endocrinology. This case demonstrates the importance of keeping hyperthyroidism on the differential for urinary frequency and polyuria without other clear etiologies.

In Reply: Most Elderly Patients With Subclinical Hypothyroidism Do Not Need To Be Treated, Risheng Xu, Nicola Abate, Nalini Ram, Kristina Little

Faculty, Staff and Students Publications

No abstract provided.

Two Spectroscopy Devices Can Approximate Fruit And Vegetable Intake In A Racially And Ethnically Diverse Sample, Stephanie B Jilcott Pitts, Qiang Wu, Melissa N Laska, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Background: Assessing fruit and vegetable intake is important to determine the effectiveness of nutrition intervention studies. Few objective measures of fruit and vegetable intake have been directly compared within the same study participants.

Objectives: This study aims to compare the relative validity of 2 different skin spectrophotometry devices to serve as biomarkers of plasma carotenoid concentrations, self-reported fruit and vegetable intake (FVI), and carotenoid intake, to examine if both devices can be used to approximate FVI.

Methods: Human skin carotenoid scores (SCS, Veggie Meter-assessed) and color space measurement data from 2 prior studies were used. Participants' skin color space parameters …

A Brief Guide To Statistical Analysis Of Grouped Data In Preclinical Research, Colby J Vorland, Lilian Golzarri-Arroyo, David B Allison

Children’s Nutrition Research Center Staff Publications

Clustering and nesting (C&N) arise in many preclinical studies such as when animals are group-housed, share litters, or in cell culture. Ignoring C&N undermines the validity of analyses. We explain how C&N arise and valid designs and analyses.

Defining Lipedema’S Molecular Hallmarks By Multi-Omics Approach For Disease Prediction In Women, Leon G Straub, Jan-Bernd Funcke, Nolwenn Joffin, Chanmin Joung, Sara Al-Ghadban, Shangang Zhao, Qingzhang Zhu, Ilja L Kruglikov, Yi Zhu, Paul R Langlais, Ruth Gordillo, Karen L Herbst, Philipp E Scherer

Children’s Nutrition Research Center Staff Publications

Lipedema is a chronic disease in females characterized by pathologic subcutaneous adipose tissue expansion and hitherto remains without druggable targets. In this observational study, we investigated the molecular hallmarks of lipedema using an unbiased multi-omics approach. We found adipokine dysregulation in lipedema patients participating in a cross-sectional clinical study (ClinicalTrial.gov, NCT02838277), pointing towards the adipocyte as a key player. Analyses of newly generated transcriptomic (SRA, PRJNA940039) and proteomic (ProteomeXchange, PXD058489) datasets of early- and late-stage lipedema samples revealed a local downregulation of factors involved in inflammation. Concomitantly, factors involved in cellular respiration, oxidative phosphorylation, as well as in mitochondrial …

The Diabetes Prevention Program And Its Outcomes Study: Niddk's Journey Into The Prevention Of Type 2 Diabetes And Its Public Health Impact, Jill P Crandall, Dana Dabelea, William C Knowler, David M Nathan, Marinella Temprosa, Dpp Research Group

Children’s Nutrition Research Center Staff Publications

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After mean 2.8 years, ILS …

Metabolic Clearance Rate Of Insulin Across The Glucose Tolerance Spectrum By Race And Ethnicity In Youth With Obesity, Wonhee Cho, Fida Bacha, Hala Tfayli, Sojung Lee, Sara F Michaliszyn, Joon Young Kim, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Objective: Despite β-cell failure in youth with dysglycemia (i.e., impaired glucose tolerance [IGT] and type 2 diabetes), fasting insulin (FI) concentrations are elevated. Herein, we examined the following: 1) metabolic clearance rate of insulin (MCRI) in youth with obesity and normal glucose tolerance (NGT) versus those with IGT versus those with type 2 diabetes; 2) racial and ethnic differences in insulin dynamics; and 3) metabolic/adiposity correlates of MCRI.

Methods: A total of 206 youth underwent assessment of fasting glucose, FI, MCRI and peripheral insulin sensitivity (PIS), first-phase insulin secretion, disposition index, body composition, and abdominal adiposity.

Results: In type 2 …

To Pause With A Cliffhanger Or A Temporary Closure? The Differential Impact Of Serial Versus Episodic Narratives On Children's Physical Activity Behaviors, Amy Shirong Lu, Melanie C Green, Caio Victor Sousa, Jungyun Hwang, I-Min Lee, Debbe Thompson, Tom Baranowski

Children’s Nutrition Research Center Staff Publications

Research has supported the effectiveness of narratives for promoting health behavior, but different narrative presentation formats (serial vs. episodic) have seldom been compared. Suspense theories suggest that serial narratives, which do not provide a full resolution at the end of an episode, may create higher motivation for continued engagement with a story. Forty-four 8 to 12-year-old children were randomly assigned to watch an animation series designed for an existing active video game in which the plot was delivered either continuously across multiple episodes (serial) or in multiple yet relatively independent self-contained episodes (episodic). Controlling for social desirability, children who watched …

Clinical Outcomes After Hospitalization For Acute Coronary Syndrome In Patients Treated With Semaglutide Versus Bariatric Surgery: A Retrospective Multicenter Analysis, Nameer Ascandar, Charles Boadu, Gauthier Stepman, George Skaf, Olugbenga Oyesanmi, Sabry Omar, Rias Ali, Michael Schandorf-Lartey

HCA Healthcare Journal of Medicine

Background

Obesity is a chronic medical condition with a rising prevalence in the United States. A wide range of morbidity and mortality is associated with obesity, with coronary artery disease being among the most common. Ischemic heart disease continues to be the primary cause of death in the United States. Taken together, interventions to minimize the detrimental effects of obesity on patients at risk of heart disease will not only benefit the patient, but the health care system as well.

Methods

In this retrospective study, we used the HCA Healthcare enterprise data warehouse to identify all adult patients who were …

Intermittent Fasting For Metabolic Syndrome Management, Tony Laborde

Lynchburg Journal of Medical Science

This paper reviews the potential of intermittent fasting as a non-pharmacological therapeutic approach to the treatment of metabolic syndrome (MetS). MetS is a global health problem with risk factors that include obesity, hypertension, hyperglycemia, low high-density lipoprotein (HDL) cholesterol, and high triglycerides that predispose to cardiovascular disease and type 2 diabetes. Traditional treatment approaches, including pharmacological agents and lifestyle modification, are typically of short-term benefit. Intermittent fasting, with its scheduled cycles of eating and fasting, presents another strategy for improving weight control, insulin sensitivity, lipid profiles, and blood pressure. Various intermittent fasting regimens, including time-restricted feeding and alternate-day fasting, have …

Efficacy And Safety Of Olezarsen In Dyslipidemia: A Systematic Review And Dose-Response Meta-Analysis Of Randomized Controlled Trials, Christopher D. Tristan, Risalina Myrtha, Matthew A. Wijayanto, Erlangga M. Kynaya, Muhammad F. Hamka, Nathania E. Sudiono, Muhammad A. Rusyidi, Muhana F. Ilyas

Journal of the Saudi Heart Association

Olezarsen emerged as a novel promising Apo-C3 inhibitor for dyslipidemia. However, its dose-response relationship remains uncertain. This review aims to evaluate the lipid-lowering effect of olezarsen, safety measures, and dose-response effects to determine the optimal dose. A systematic search was conducted across Scopus, PubMed, ScienceDirect, and CENTRAL on January 2, 2025. Randomized controlled trial (RCT) comparing olezarsen with placebo in dyslipidemia was included. The Rob 2.0 tool was implemented to assess quality. R-studio and STATA were used to conduct statistical analysis. From a total of 194 documents at initial search, four RCTs involving 361 patients were included in the present …

The Maturity-Onset Diabetes Of The Young (Mody) Calculator Overestimates Mody Probability In Hispanic Youth, Guido Alarcon, Anh Nguyen, Angus Jones, Beverley Shields, Maria J Redondo, Mustafa Tosur

Children’s Nutrition Research Center Staff Publications

Context: The applicability of the maturity-onset diabetes of the young (MODY) risk calculator to non-White European populations remains unknown.

Objective: We aimed to test its real-world application in Hispanic youth.

Methods: We conducted a retrospective chart review of Hispanic youth (< 23 years) with diabetes (n = 2033) in a large pediatric tertiary care center in the United States. We calculated MODY probability for all subjects, splitting them into 2 cohorts based on the original model: individuals who were started on insulin within 6 months of diabetes diagnosis (Cohort 1) and those who were not (Cohort 2).

Results: Cohort 1 consisted of 1566 individuals (median age [25p, 75p]: 16 [13, 19] years, 49% female), while Cohort 2 comprised 467 youth (median age [25p, 75p]: 17 [15, 20] years, 62% female). The mean MODY probability was 5.9% and 61.9% in Cohort 1 and Cohort 2, respectively. The mean probability for both cohorts combined was 18.8%, suggesting an …

Attitudes Toward Pig Islet Xenotransplantation For Type 1 Diabetes: A Scoping Review, Daniel J Hurst, Daniel Rodger, Luz A Padilla, Fernando Ovalle

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Over 8 million people globally have type 1 diabetes. Islet allotransplantation offers an alternative to insulin therapy but is constrained by donor availability. Genetically modified pig islet transplantation presents a potential solution, yet understanding stakeholder attitudes is crucial before clinical adoption.

METHODS: This scoping review followed Joanna Briggs Institute methodology and PRISMA guidelines. CINAHL, EMBASE, PubMed, PsychINFO, and SCOPUS were searched for studies examining attitudes toward pig islet xenotransplantation among patients, healthcare workers, and other stakeholders.

RESULTS: From 199 sources, 16 met eligibility criteria, spanning ten countries from 2003 to 2023. The 23,780 participants included 1,535 (6.5%) patients/family members, …

Common Aav Gene Therapy Vectors Show Nonselective Transduction Of Ex Vivo Human Brain Tissue, J P Mcginnis, Joshua Ortiz-Guzman, Maria Camila Guevara, Sai Mallannagari, Benjamin D W Belfort, Suyang Bao, Snigdha Srivastava, Maria Morkas, Emily Ji, Angela Addison, Evelyne K Tantry, Sarah Chen, Ying Wang, Zihong Chen, Kalman A Katlowitz, Jeffrey J Lange, Melissa M Blessing, Carrie A Mohila, M Cecilia Ljungberg, Guillermo Aldave, Ali Jalali, Akash Patel, Sameer A Sheth, Howard L Weiner, Shankar Gopinath, Ganesh Rao, Akdes Serin Harmanci, Daniel J Curry, Benjamin R Arenkiel

Children’s Nutrition Research Center Staff Publications

The ability to deliver a therapeutic sequence to a specific cell type in the human brain would make possible innumerable therapeutic options for some of our most challenging diseases; however, studies on adeno-associated virus (AAV) vector tropism have generally relied on animal models with limited translational utility. For this reason, establishing the tropism of common adeno-associated virus (AAV) vectors in living human brain tissue serves as an important baseline for further optimization, as well as a determination of human brain cell types transduced by clinically approved gene therapy vectors AAV2 and AAV9. We have adapted an

Why Acromegaly Dies: A Systematic Review, Isam Noori Salman, Safaa Ehssan Atta, Baydaa Ahmed Abed, Noor Ulhuda G. Mohammed

Maaen Journal for Medical Sciences

Acromegaly is a rare endocrine clinical syndrome characterized by long-term elevated production of growth hormone (GH) due to a pituitary adenoma tumor. The main problem of acromegaly patients (AC-PTs) is prolonged elevated GH concentration, which leads to increased insulin-like growth factor 1 (IGF-1) production, causing the characteristic tissue and bone overgrowth. The appearance of diabetes in AC-PTs was linked with the high risks of cardiovascular morbidity, indicating that individuals with both conditions face heightened health challenges. Acromegaly typically has a higher cancer incidence rather than the general population. Without early diagnosis and effective treatment, excess GH can have widespread systemic …

Determining Accurate Pore Structures Of Polypropylene Membrane For Ecmo Using Fe-Sem Under Optimized Conditions, Makoto Fukuda, Yoshiaki Nishite, Eri Murata, Koki Namekawa, Tomohiro Mori, Tsutomu Tanaka, Kiyotaka Sakai

Children’s Nutrition Research Center Staff Publications

Long-term ECMOs are expected to be put into practical use in order to prepare for the next emerging severe infectious diseases after the novel coronavirus pandemic in 2019-2023. While polypropylene (PP) and polymethylpentene (PMP) are currently the mainstream materials for the hollow fiber membranes of ECMO, the PP membrane coated with a silicone layer on the outer surface has also been commercialized. In this study, we sought a method to accurately observe the detailed pore morphologies of the PP membrane by suppressing irreversible changes in the morphology in SEM observation, which is a general-purpose observation with higher resolution. As a …

Effects Of Cerebral Tumor Necrosis Factor Alpha On Systemic Glucose Homeostasis In Obese Mice, Gabriela Griepp

Honors Projects

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired blood glucose regulation and persistent hyperglycemia. The central nervous system functions as a key regulator in the maintenance of peripheral normoglycemia. Obesity, commonly associated with T2DM, often leads to chronic inflammation in the hypothalamus, a critical brain center for integrating metabolic feedback and controlling outputs to peripheral organs. However, the physiological mechanisms through which obesity-induced brain inflammation affects glucose regulation remain somewhat unclear. Previous studies have linked one key pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α), to metabolic function and glycemic control; however, the exact nature of its …

Present And Future Of Microbiome-Targeting Therapeutics, Lauren E Lynch, Rachel Lahowetz, Christian Maresso, Austen Terwilliger, Jason Pizzini, Valeria Melendez Hebib, Robert A Britton, Anthony W Maresso, Geoffrey A Preidis

Children’s Nutrition Research Center Staff Publications

A large body of evidence suggests that single- and multiple-strain probiotics and synbiotics could have roles in the management of specific gastrointestinal disorders. However, ongoing concerns regarding the quality and heterogeneity of the clinical data, safety in vulnerable populations, and the lack of regulation of products containing live microbes are barriers to widespread clinical use. Safety and regulatory issues must be addressed and new technologies considered. One alternative future strategy is the use of synthetic bacterial communities, defined as manually assembled consortia of two or more bacteria originally derived from the human gastrointestinal tract. Synthetic bacterial communities can model functional, …

Diabetes-Related Distress Over Time And Its Associations With Glucose Levels In School-Aged Children., Susana R. Patton, Nicole Kahhan, Amy Milkes, Ryan J. Mcdonough, Matthew Benson, Mark A. Clements, Jessica S. Pierce

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: In a cohort of families of school-age children (8-12.99 years old) with type 1 diabetes, we examined the stability of parent and child diabetes-related distress (DRD) over 6 months and the associations between parent and child DRD and child glycated hemoglobin (HbA1c) over time.

RESEARCH DESIGN AND METHODS: We recruited families from two large pediatric hospital systems in the USA and used validated measures of parent (Parent Problem Areas in Diabetes-Child, PPAID-C) and child (Problem Areas in Diabetes-Child, PAID-C) DRD and children's HbA1c. We collected data at baseline and 6 months. We calculated minimal clinically important differences in PPAID-C …

Changes In The Fxr-Cistrome And Alterations In Bile Acid Physiology In Wilson Disease, Clavia Ruth Wooton-Kee, Hari K Yalamanchili, Islam Mohamed, Manal Hassan, Kenneth D R Setchell, Monica Narvaez Rivas, Ayse K Coskun, Vasanta Putluri, Nagireddy Putluri, Prasun Jalal, Michael L Schilsky, David D Moore

Children’s Nutrition Research Center Staff Publications

Background: Wilson disease (WD) is an autosomal recessive disorder that results in excessive hepatic copper, causing hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver failure. Previous studies have revealed dysregulation of many farnesoid X receptor (FXR) metabolic target genes in WD, including the bile salt exporter pump, the major determinant of bile flow.

Methods: We tested the hypothesis that the FXR-cistrome is decreased in Atp7b-/- mice in accord with dysregulated bile acid homeostasis.

Results: FXR binding within Atp7b-/- mouse livers displayed surprising complexity: FXR binding was increased in distal intergenic regions but decreased in promoter regions in Atp7b-/- versus wild-type mice. …

Bile Acid Regulation Of Xenobiotic Nuclear Receptors On The Expressions Of Orosomucoids In The Liver, Ji Ho Suh, Inyoung Cheon, Hyun-Jung Jung, Sung Ho Lee, Mi Jeong Heo, Matthew Deberge, Clavia Ruth Wooton-Kee, Kang Ho Kim

Children’s Nutrition Research Center Staff Publications

The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic nuclear receptors activated by various xenobiotics, drugs, hormones, and bile acids (BAs). Upon activation, these nuclear receptors play critical roles in regulating systemic energy homeostasis. However, precise mechanisms through which CAR and PXR influence systemic metabolism remain incompletely understood. Here, we investigated the impact of CAR and PXR on the liver-secreted hormone (i.e., hepatokine) expressions in response to BA stress such as cholic acid (CA) feeding. Our analysis revealed that several BA-activated genes, including the well-known CAR/PXR target, aldo-keto reductase family 1, member B7 (Akr1b7 …