Biochemical Phenomena, Metabolism, and Nutrition Commons^™

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 …

Cazyme Gene Cluster Diversity In Human Gut Microbiome, Yi Xing

Department of Food Science and Technology: Dissertations, Theses, and Student Research

In gut microbiome research, carbohydrate-active enzyme gene clusters (CGCs) have emerged as key functional units for understanding microbial glycan degradation. Unlike taxonomic or broad pathway annotations, CGCs offer gene-cluster-level resolution and capture substrate-specific microbial functions. However, their diversity and distribution in relation to host metabolic phenotypes, such as obesity, remain poorly characterized. This study tests the hypothesis that the composition and abundance of fiber-targeting CGCs vary between obese and healthy human gut microbiomes, reflecting distinct microbial carbohydrate utilization strategies. To examine this, we constructed a high-quality reference CGC dataset comprising 94,019 clusters from the Unified Human Gastrointestinal Genome and profiled …

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 …

Functional Regulation Of Macrophages By Ces1d-Mediated Lipid Signaling In Immunometabolism, Long J Shao, Fathima Elizondo, Feng Gao, Rabie Habib, Xin Li, Katherine Pham, Jazmin Ysaguirre, Maryam Elizondo, Shirindokht Shirazi, Kristin L Eckel-Mahan, Sean Hartig, Huaizhu Wu, Kai Sun

Faculty, Staff and Student Publications

Objective: Macrophage accumulation in metabolically active tissues during obesity is common in both animals and humans, but the lipid signaling mechanisms that trigger macrophage inflammation remain unclear. This study investigates the role of Ces1d, an unconventional lipase, in regulating macrophage inflammation under nutritional stress.

Methods: A myeloid-specific Ces1d knockout (LysM-Cre-Ces1d floxed/floxed, KO) mouse model was used for the studies. For in vitro tests, bone marrow-derived macrophages (BMDMs) from control (Ces1d floxed/floxed, WT) and KO mice were assessed for migration, polarization, and activation. For in vivo experiments, WT and KO mice were induced to obesity via a high-fat diet (HFD) and …

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 …

Muscle Rev-Erb Controls Time-Dependent Adaptations To Chronic Exercise In Mice, Jidong Liu, Fang Xiao, Abhinav Choubey, Udhaya Kumar S, Yanxiang Wang, Sungguan Hong, Tingting Yang, Husniye Gul Otlu, Ege Sanem Oturmaz, Emanuele Loro, Yuxiang Sun, Pradip Saha, Tejvir S Khurana, Li Chen, Xinguo Hou, Zheng Sun

Center on Aging Staff Publications

The best time of the day for chronic exercise training and the mechanism underlying the timing effects is unclear. Here, we show that low-intensity, low-volume treadmill training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance. Baseline muscle performance also exhibits diurnal variations, with higher strength but lower endurance before sleep than after waking. Muscle-specific knockout of circadian clock genes Rev-erbα/β (Rev-MKO) in male mice eradicates the diurnal variations in both training and baseline conditions without affecting muscle mass, mitochondrial content, food intake, or spontaneous activities. Multi-omics and metabolic measurements reveal …

Peran Prediktif Il-6, Il-10, Dan Tnf-Α Plasma Terhadap Gagal Ginjal Akut Pada Pasien Dengan Covid-19 Derajat Sedang Dan Berat, Dewi Gathmyr, Maruhum Bonar H Bonar, Adityo Susilo, Kuntjoro Harimurti, Ginova Nainggolan, Alvin Tagor, Hamzah Shatri, Cosmas Rinaldi Adithya Lesmana, Zulkifli Amin

Jurnal Penyakit Dalam Indonesia

Introduction. Acute kidney injury (AKI) is associated with higher mortality rate in COVID-19 patients due to inflammation and immune dysregulation. This study aimed to correlate serum levels of IL-6, IL-10, and TNF-α with serum creatinine changes and their roles to predict incidence of acute kidney injury (AKI) in patients with moderate and severe COVID-19.

Methods. This prospective cohort study was conducted among patients with moderate to severe COVID-19 in Pertamina Central Hospital Jakarta, Indonesia during November 2020 to January 2021. All serum levels of cytokines (IL-6, IL-10, and TNF-α) and creatinine were collected on the first day and …

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 …

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

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 …

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, …

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 …

Time To Weight Plateau With Tirzepatide Treatment In The Surmount-1 And Surmount-4 Clinical Trials, Deborah B Horn, Scott Kahan, Rachel L Batterham, Dachuang Cao, Clare J Lee, Madhumita Murphy, Sylvia Gonsahn-Bollie, Farai Chigutsa, Adam Stefanski, Julia P Dunn

Faculty, Staff and Student Publications

The rate of weight reduction during obesity treatment declines over time and eventually reaches a weight plateau. We investigated factors associated with time to weight plateau (TTWP) in tirzepatide-treated participants with obesity or overweight in a post-hoc analysis of SURMOUNT-1 and SURMOUNT-4 trials. Participants adherent to tirzepatide treatment and achieving ≥5% weight loss by primary endpoint (week 72 SURMOUNT-1; week 88 SURMOUNT-4) were included. Weight plateau was defined as a weight change < 5% over a 12-week interval and all subsequent 12-week intervals. TTWP was time from randomization to the start of the first 12-week interval. Association between baseline characteristics and TTWP was assessed. Overall, 1438 participants in SURMOUNT-1 and 259 in SURMOUNT-4 were included. Across BMI categories (overweight, class I, II, and III), median TTWP in SURMOUNT-1 was 24.3, 26.0, 36.1, and 36.1 weeks, respectively (p < .05, class II and III vs. overweight). By week 72, 90.2%, 88.9%, 87.6%, and 87.8% of participants in SURMOUNT-1 had reached a weight plateau across respective BMI categories [Correction added on 22 January 2025, after first online publication: The "72%" has been changed to "72" in this version.]. Higher doses of tirzepatide (10/15 mg), younger age, and female sex were more likely to reach a weight plateau later. Results in SURMOUNT-4 were similar. In this post-hoc analysis, most participants reached a weight plateau by week 72. Higher doses of tirzepatide, younger age, and female sex were associated with a longer TTWP. Further research into modifiers of weight reduction phases with tirzepatide may inform treatment decisions for its use in chronic weight management. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT04184622 (SURMOUNT-1) and NCT04660643 (SURMOUNT-4), available at http://www.clinicaltrials.gov/.

The Impact Of Narratives And Active Video Games Among Black And Hispanic Children With Overweight And Obesity: A Randomized Controlled Trial, Amy S Lu, Tom Baranowski, Tiago V Barreira, Amy Fleischman, Melanie C Green, Shirley Y Huang, I-Min Lee, Lynne L Levitsky, Farzad Noubary, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: Overweight and obesity disproportionately affect Black and Hispanic children who also play more video games. Narratives, coupled with home-based active video games (AVGs), may enhance PA and mitigate these disparities. This study tested the effect of narrative-enhanced home-based AVGs among predominantly Black and Hispanic children with overweight and obesity.

Methods: This 6-month three-group RCT recruited 135 children aged 7-14 from pediatric clinics in Boston, MA (January 2020 - May 2022) during the COVID-19 pandemic. Participants were randomized into: [Narrative + AVG], receiving an Xbox/Kinect with six AVGs interspersed with a narrative animation Ataraxia (72 episodes over six months), which …

“Non-Markovian” And “Directional” Errors Inhibit Scientific Self-Correction And Can Lead Fields Of Study Astray: An Illustration Using Gardening And Obesity-Related Outcomes, Jon Agley, Sarah E Deemer, David B Allison

Children’s Nutrition Research Center Staff Publications

Herein we coin the terms non-Markovian error and biased Markovian error to describe categories of scientific errors for which general progress within a field of study may be unlikely to result in scientific self-correction. We provide examples of such errors and show their impact on studies about gardening and obesity.