Biochemical Phenomena, Metabolism, and Nutrition Commons^™

The Chromosome-Level Rambutan Genome Reveals A Significant Role Of Segmental Duplication In The Expansion Of Resistance Genes, Jinfang Zheng1, Lyndel W. Meinhardt, Ricardo Goenaga, Tracie Matsumoto, Dapeng Zhang, Yanbin Yin

Food for Health: Publications

Rambutan (Nephelium lappaceum var. lappaceum), a tropical fruit tree native to southeastern Asia, belongs to the family Sapindaceae. Rambutan is a popular table fruit and is also processed into preserves, juices, wines, and sorbets [1]. At present, only three Sapindaceae genomes are publicly available: Xanthoceras sorbifolium [2], Dimocarpus longan (longan) [3], and Acer yangbiense [4]. During the process of submitting this manuscript, the genome paper for the rambutan cultivar Baoyan7 became available online, but its genome sequence has not yet been released [5].

Protein Tyrosine Phosphatase Receptor Δ Serves As The Orexigenic Asprosin Receptor, Ila Mishra, Wei Rose Xie, Juan C Bournat, Yang He, Chunmei Wang, Elizabeth Sabath Silva, Hailan Liu, Zhiqiang Ku, Yinghua Chen, Bernadette O Erokwu, Peilin Jia, Zhongming Zhao, Zhiqiang An, Chris A Flask, Yanlin He, Yong Xu, Atul R Chopra

Faculty, Staff and Student Publications

Asprosin is a fasting-induced glucogenic and centrally acting orexigenic hormone. The olfactory receptor Olfr734 is known to be the hepatic receptor for asprosin that mediates its effects on glucose production, but the receptor for asprosin's orexigenic function has been unclear. Here, we have identified protein tyrosine phosphatase receptor δ (Ptprd) as the orexigenic receptor for asprosin. Asprosin functions as a high-affinity Ptprd ligand in hypothalamic AgRP neurons, regulating the activity of this circuit in a cell-autonomous manner. Genetic ablation of Ptprd results in a strong loss of appetite, leanness, and an inability to respond to the orexigenic effects of asprosin. …

Metabolic Inflexibility In Youth With Obesity: Is It A Feature Of Obesity Or Distinctive Of Youth Who Are Metabolically Unhealthy?, Nour Y Gebara, Joon Young Kim, Fida Bacha, Sojung Lee, Silva Arslanian

Faculty, Staff and Students Publications

Individuals with obesity have metabolic inflexibility with diminished fasting fat oxidation and blunted increase in respiratory quotient (RQ) in insulin-stimulated states. However, it is unclear if metabolic inflexibility is a characteristic of obesity per se or is unique to youth who have metabolically unhealthy obesity (MUO) compared with metabolically healthy obesity (MHO). We investigated metabolic flexibility in youth with MUO, MHO and normal weight (NW) and compared their metabolic characteristics. Youth (n = 188) were divided, based on cut-off points for in vivo insulin sensitivity (IS) of adolescents with NW, into 137 with MUO and 51 with MHO. Fasting hepatic …

Examining 24-Hour Activity And Sleep Behaviors And Related Determinants In Latino Adolescents And Young Adults With Obesity, Erica G Soltero, Neeku Navabi, Kiley B Vander Wyst, Edith Hernandez, Felipe G Castro, Stephanie L Ayers, Jenny Mendez, Gabriel Q Shaibi

Children’s Nutrition Research Center Staff Publications

Background.

Few studies have examined 24-hour activity and sleep behaviors and their contribution to type 2 diabetes (T2D) in Latino adolescents and young adults with obesity.

Aim.

This study included quantitative data on T2D risk and 24-hour activity and sleep behaviors and qualitative data on individual, social, and environmental behavioral determinants.

Method.

A 7 day, 24-hour, wrist-worn accelerometer protocol assessed moderate-to-vigorous physical activity (PA), sedentary behaviors (SB), sleep, and sleep regularity, in adolescents (N = 38; 12–16 years) and young adults (N = 22; 18–22 years). T2D-related outcomes included adiposity (BMI, BF%, waist circumference), fasting, and 2-hour glucose. …

Food Assistance Use Among Food Bank Clients Affected By Type 2 Diabetes, Eliza Short, Jayati Sharma, Debbe I Thompson, Douglas Taren, Rhonda Gonzalez, Melanie Hingle

Children’s Nutrition Research Center Staff Publications

Objective: To understand the perspectives of food bank clients affected by type 2 diabetes (T2DM).

Design: Semi-structured in-depth interviews conducted with food bank clients.

Setting: Arizona regional food bank.

Participants: Twenty English- and Spanish-speaking food bank clients with T2DM or living with a person with T2DM, aged 45-83 years, majority female, Hispanic, and food insecure.

Phenomenon of interest: Food bank use and preferences, and how these related to T2DM management.

Analysis: A hybrid thematic analysis combining inductive and deductive reasoning.

Results: Three organizing themes emerged from the analysis. First, food assistance was influenced by food preferences and the ability to …

Trans Fatty Acid Biomarkers And Incident Type 2 Diabetes: Pooled Analysis Of 12 Prospective Cohort Studies In The Fatty Acids And Outcomes Research Consortium (Force), Heidi T M Lai, Fumiaki Imamura, Andres V Ardisson Korat, Rachel A Murphy, Nathan Tintle, Julie K Bassett, Jiaying Chen, Janine Kröger, Kuo-Liong Chien, Mackenzie Senn, Alexis C Wood, Nita G Forouhi, Matthias B Schulze, William S Harris, Ramachandran S Vasan, Frank Hu, Graham G Giles, Allison Hodge, Luc Djousse, Ingeborg A Brouwer, Frank Qian, Qi Sun, Jason H Y Wu, Matti Marklund, Rozenn N Lemaitre, David S Siscovick, Amanda M Fretts, Aladdin H Shadyab, Joann E Manson, Barbara V Howard, Jennifer G Robinson, Robert B Wallace, Nick J Wareham, Yii-Der Ida Chen, Jerome I Rotter, Michael Y Tsai, Renata Micha, Dariush Mozaffarian, Fatty Acids And Outcomes Research Consortium (Force)

Children’s Nutrition Research Center Staff Publications

Objective: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.

Research design and methods: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using …

Identification Of Genetic Loci Simultaneously Associated With Multiple Cardiometabolic Traits, Alexis C Wood, Amit Arora, Michelle Newell, Victoria L Bland, Jin Zhou, Nicola Pirastu, Jose M Ordovas, Yann C Klimentidis

Children’s Nutrition Research Center Staff Publications

Background and aims: Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits.

Methods and results: We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574-456,823). Multiple …

Β-Carotene Oxygenase 2 Genotype Modulates The Impact Of Dietary Lycopene On Gene Expression During Early Tramp Prostate Carcinogenesis, Nancy E Moran, Jennifer M Thomas-Ahner, Joshua W Smith, Ceasar Silva, Noor A Hason, John W Erdman, Steven K Clinton

Children’s Nutrition Research Center Staff Publications

Background: Epidemiologic studies suggest lycopene and tomato intake are inversely associated with human prostate cancer incidence. In the genetically driven murine prostate carcinogenesis model transgenic adenocarcinoma of the mouse prostate (TRAMP), prostate cancer is inhibited by feeding of lycopene or tomatoes, and these effects are modulated by the β-carotene oxygenase 2 (Bco2) genotype.

Objective: We sought insight into this interaction through evaluation of prostate gene expression patterns during early TRAMP carcinogenesis.

Methods: Three-week-old TRAMP/+ or TRAMP/- × Bco2+/+ or Bco2-/- mice were fed a control, lycopene beadlet, or 10% tomato powder-containing semipurified diet (providing 0, 384 and 462 mg lycopene/kg …

Metabolic Inflexibility In Youth With Obesity: Is It A Feature Of Obesity Or Distinctive Of Youth Who Are Metabolically Unhealthy?, Nour Y Gebara, Joon Young Kim, Fida Bacha, Sojung Lee, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Background:

Individuals with obesity have metabolic inflexibility with diminished fasting fat oxidation and blunted increase in respiratory quotient (RQ) in insulin-stimulated states. However, it is unclear if metabolic inflexibility is a characteristic of obesity per se or is unique to youth who have metabolically unhealthy obesity (MUO) compared with metabolically healthy obesity (MHO).

Objective:

We investigated metabolic flexibility in youth with MUO, MHO and normal weight (NW) and compared their metabolic characteristics.

Patients/Design:

Youth (n=188) were divided, based on cut-off points for in vivo insulin sensitivity (IS) of adolescents with NW, into 137 with MUO and 51 with MHO. Fasting …

Determining The Genomic Localization And Binding Partners Of Zinc Finger Protein 410, Mariko Locke

Senior Honors Theses

The results of a folate deficiency study affecting cognition in mice suggested the altered genes may be controlled by a transcription factor known as Zinc Finger Protein 410 (Zfp410). Due to a lack of literature on Zfp410’s interacting proteins and DNA-binding location, our study aims to further elucidate the role Zfp410 plays in affecting cognition. A custom antibody was used to determine the Zfp410 isoforms present in mouse and rat brains. Moreover, the antibody was used to determine the binding partners of Zfp410 in the brain and locate specific genomic regions/sequences with which it associates in vivo. These results may …

Changes In Physical Activity Associated With The Covid-19 Pandemic In Individuals With Overweight And Obesity: An Interrupted Time Series Analysis With Historical Controls, Michael C Robertson, Che Young Lee, Ivan Haw-Chong Wu, Yue Liao, Margaret Raber, Nathan Parker, Thuan Le, Leticia Gatus, Karen M Basen-Engquist

Faculty, Staff and Students Publications

The objective of this study was to investigate changes in physical activity patterns associated with the COVID-19 pandemic in individuals with overweight and obesity who were participating in a school district worksite weight loss program. We conducted comparative design interrupted time series analyses on physical activity device (Fitbit) data from the 2018-2019 and 2019-2020 school years (N = 211). We administered a questionnaire in 2020 to supplement device data. After the stay-at-home orders in 2020, participants tended to decrease their weekly step count (B = -1315.7, SE = 627.7, p = .045), decrease their weekly "Lightly active minutes" (B = …

Colonic Epithelial Angiotensin-Converting Enzyme 2 (Ace2) Expression In Blacks And Whites: Potential Implications For Pathogenesis Covid-19 Racial Disparities, Mart De La Cruz, David P Nunes, Vaishali Bhardwaj, Deepika Subramanyan, Caroline Zaworski, Priya Roy, Hemant K Roy

Faculty, Staff and Students Publications

BACKGROUND: Covid-19 toll is disproportionate in Blacks although the mechanisms remain incompletely understood. From a biological perspective, several host proteins have received most attention as logical susceptibility targets. Specifically, angiotensin-converting enzyme 2 (ACE2) serves as the epithelial cell receptor and acts in concert with transmembrane protease serine 2 (TMPRSS2). Intriguingly, ACE2 can also suppress the inflammatory response and therefore may impact the severity of Covid-19 infections (from the exuberant immune response a.k.a. "cytokine storm"). We, therefore, assessed expression of ACE2 and TMPRSS2 in Blacks versus Whites.

METHODS: Archived mucosal biopsies from colonoscopic biopsies of visually normal rectal mucosa without concurrent …

Prevalence Of Metabolic Syndrome Among The Adult Population In Western China And The Association With Socioeconomic And Individual Factors: Four Cross-Sectional Studies, Xinyin Xu, Jing Zeng, Wei Yang, Ting Dong, Xin Zhang, Shuwen Cheng, Xiaobo Zhou, Maigeng Zhou, Ling Niu, Guanghui Yi, You Li, Lishi Zhang, Yin Deng, Xianping Wu

Faculty, Staff and Student Publications

Objectives: This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation.

Design: Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015.

Setting: From 2010 to 2018, 8-15 counties/districts of West China were included.

Participants: A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors.

Results: …

Development And Characterization Of Anti-Galectin-9 Antibodies That Protect T Cells From Galectin-9-Induced Cell Death, Riyao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Weiya Xia, Boning Liu, Yu-Yi Chu, Laura Bover, Long Vien, Mien-Chie Hung

Faculty, Staff and Student Publications

Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a β-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain-containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two …

Vitamin C Reduces Igf-1 And Vegf Signaling In Retinal Endothelial Cells, Jonathon Reynolds

Annual Research Symposium

No abstract provided.

An Objective System For Quantitative Assessment Of Television Viewing Among Children (Family Level Assessment Of Screen Use In The Home-Television): System Development Study, Anil Kumar Vadathya, Salma Musaad, Alicia Beltran, Oriana Perez, Leo Meister, Tom Baranowski, Sheryl O Hughes, Jason A Mendoza, Ashutosh Sabharwal, Ashok Veeraraghavan, Teresia O'Connor

Children’s Nutrition Research Center Staff Publications

Background: Television viewing among children is associated with developmental and health outcomes, yet measurement techniques for television viewing are prone to errors, biases, or both.

Objective: This study aims to develop a system to objectively and passively measure children's television viewing time.

Methods: The Family Level Assessment of Screen Use in the Home-Television (FLASH-TV) system includes three sequential algorithms applied to video data collected in front of a television screen: face detection, face verification, and gaze estimation. A total of 21 families of diverse race and ethnicity were enrolled in 1 of 4 design studies to train the algorithms and …

Identification Of The Global Mir-130a Targetome Reveals A Role For Tbl1xr1 In Hematopoietic Stem Cell Self-Renewal And T(8; 21) Aml, Gabriela Krivdova, Veronique Voisin, Erwin M Schoof, Sajid A Marhon, Alex Murison, Jessica L Mcleod, Martino M Gabra, Andy G X Zeng, Stefan Aigner, Brian A Yee, Alexander A Shishkin, Eric L Van Nostrand, Karin G Hermans, Aaron C Trotman-Grant, Nathan Mbong, James A Kennedy, Olga I Gan, Elvin Wagenblast, Daniel D De Carvalho, Leonardo Salmena, Mark D Minden, Gary D Bader, Gene W Yeo, John E Dick, Eric R Lechman

Faculty, Staff and Students Publications

Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells (HSCs) point to shared core stemness properties. However, discordance between mRNA and protein signatures highlights an important role for post-transcriptional regulation by microRNAs (miRNAs) in governing this critical nexus. Here, we identify miR-130a as a regulator of HSC self-renewal and differentiation. Enforced expression of miR-130a impairs B lymphoid differentiation and expands long-term HSCs. Integration of protein mass spectrometry and chimeric AGO2 crosslinking and immunoprecipitation (CLIP) identifies TBL1XR1 as a primary miR-130a target, whose loss of function phenocopies miR-130a overexpression. Moreover, we report that miR-130a is highly expressed …

Pufa Ω-3 And Ω-6 Biomarkers And Sleep: A Pooled Analysis Of Cohort Studies On Behalf Of The Fatty Acids And Outcomes Research Consortium (Force), Rachel A Murphy, Nathan Tintle, William S Harris, Maryam Darvishian, Matti Marklund, Jyrki K Virtanen, Sari Hantunen, Vanessa D De Mello, Jaakko Tuomilehto, Jaana Lindström, Matthew A Bolt, Ingeborg A Brouwer, Alexis C Wood, Mackenzie Senn, Susan Redline, Michael Y Tsai, Vilmundur Gudnason, Gudny Eiriksdottir, Eva Lindberg, Aladdin H Shadyab, Buyun Liu, Mercedes Carnethon, Matti Uusitupa, Luc Djousse, Ulf Risérus, Lars Lind, Rob M Van Dam, Woon-Puay Koh, Peilin Shi, David Siscovick, Rozenn N Lemaitre, Dariush Mozaffarian

Children’s Nutrition Research Center Staff Publications

BACKGROUND: n-3 and n-6 PUFAs have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters.

OBJECTIVES: We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium.

METHODS: Harmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts. Participants were 35-96 y old and from 5 nations. Circulating measures included α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), DHA, EPA + DPA + DHA, linoleic acid, and arachidonic acid. Sleep duration (10 …

Prolonged Glycemic Adaptation Following Transition From A Low- To High-Carbohydrate Diet: A Randomized Controlled Feeding Trial, Lisa T Jansen, Nianlan Yang, Julia M W Wong, Tapan Mehta, David B Allison, David S Ludwig, Cara B Ebbeling

Children’s Nutrition Research Center Staff Publications

Objective: Consuming ≥150 g/day carbohydrate is recommended for 3 days before an oral glucose tolerance test (OGTT) for diabetes diagnosis. For evaluation of this recommendation, time courses of glycemic changes following transition from a very-low-carbohydrate (VLC) to high-carbohydrate diet were assessed with continuous glucose monitoring (CGM).

Research design and methods: After achieving a weight loss target of 15% (±3%) on the run-in VLC diet, participants (18-50 years old, BMI ≥27 kg/m2) were randomly assigned for 10 weeks to one of three isoenergetic diets: VLC (5% carbohydrate and 77% fat); high carbohydrate, high starch (HC-Starch) (57% carbohydrate and 25% fat, including …

Evaluation Of The Type I Error Rate When Using Parametric Bootstrap Analysis Of A Cluster Randomized Controlled Trial With Binary Outcomes And A Small Number Of Clusters, Lilian Golzarri-Arroyo, Stephanie L Dickinson, Yasaman Jamshidi-Naeini, Roger S Zoh, Andrew W Brown, Arthur H Owora, Peng Li, J Michael Oakes, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Cluster randomized controlled trials (cRCTs) are increasingly used but must be analyzed carefully. We conducted a simulation study to evaluate the validity of a parametric bootstrap (PB) approach with respect to the empirical type I error rate for a cRCT with binary outcomes and a small number of clusters.

Methods: We simulated a case study with a binary (0/1) outcome, four clusters, and 100 subjects per cluster. To compare the validity of the test with respect to error rate, we simulated the same experiment with K=10, 20, and 30 clusters, each with 2,000 simulated datasets. To test the null …