Endocrinology, Diabetes, and Metabolism Commons^™

Increased Plasma Branched Short-Chain Fatty Acids And Improved Glucose Homeostasis: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Arianne Aslamy, Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Patricia A Sheridan, Kari E Wong, Gautam Ramesh, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi

Faculty, Staff and Students Publications

Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs. We observed a bimodal distribution of …

Ketamine For Pain In Sickle Cell Disease Reduces Opioid Usage, Christina O Onyebuchi, Corrie E Chumpitazi, Jennifer L Placencia, Andrea N Jackson, Jennifer L Jones, Laura Torres, Venée N Tubman

Faculty, Staff and Students Publications

CONTEXT: Pain attributable to sickle cell disease (SCD) is often unpredictable, recurrent, and requires complex treatments. Subanesthetic ketamine infusion has been studied in other diseases and disorders, but there is still limited data on its efficacy in pain management for SCD.

OBJECTIVES: The primary objective is to determine if subanesthetic ketamine infusion reduces pain scores and opioid requirements in hospitalized pediatric patients with SCD.

RESULTS: Forty-six admissions among 22 patients between February 2018 and December 2019 were analyzed. We observed decrease in pain scores within 24 hours of ketamine initiation in 34 of 46 admissions (mean pain score per patient …

International Consensus Statement On The Radiological Evaluation Of Dysraphic Malformations Of The Spine And Spinal Cord, Ankit Balani, Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Özgür Öztekin, Valeria Capra, Martin Catala, Andrew J Copp, Neetu Kumar, Navroop Johal, M Zubair Tahir, Dominic Thompson, Dachling Pang, David M Mirsky, Mai-Lan Ho, Thierry A G M Huisman, Andrea Rossi, Kshitij Mankad

Children’s Nutrition Research Center Staff Publications

Dysraphic malformations of the spine and spinal cord (DMSSC) represent a spectrum of common congenital anomalies typically (though not exclusively) affecting the lower spinal segments. These may be responsible for varying degrees of neurologic, orthopedic, and urologic morbidity. With advances in neuroimaging, it is now possible to better diagnose and evaluate these disorders both prenatally and postnatally. Neuroimaging, performed at the right time and with technique optimization, is integral in guiding clinical management. However, the terminology used to describe these lesions has become increasingly confusing, and there is a lack of consensus regarding the essential radiologic features and their clinical …

Parental Age Effects And Rett Syndrome, Xiaolan Fang, Lauren M Baggett, Raymond C Caylor, Alan K Percy, Jeffrey L Neul, Jane B Lane, Daniel G Glaze, Tim A Benke, Eric D Marsh, Kathleen J Motil, Judy O Barrish, Fran E Annese, Steven A Skinner

Children’s Nutrition Research Center Staff Publications

Rett syndrome (RTT) is a progressive neurodevelopmental disorder, and pathogenic Methyl-CpG-binding Protein 2 (MECP2) variants are identified in >95% of individuals with typical RTT. Most of RTT-causing variants in MECP2 are de novo and usually on the paternally inherited X chromosome. While paternal age has been reported to be associated with increased risk of genetic disorders, it is unknown whether parental age contributes to the risk of the development of RTT. Clinical data including parental age, RTT diagnostic status, and clinical severity are collected from 1226 participants with RTT and confirmed MECP2 variants. Statistical analyses are performed using Student t-test, …

Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium

Faculty, Staff and Students Publications

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( …

Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.

OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.

METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs …

Glucose Metabolism In Posterior Cingulate Cortex Has Supplementary Value To Predict The Progression Of Cognitively Unimpaired To Dementia Due To Alzheimer’S Disease: An Exploratory Study Of 18f-Fdg-Pet, Qi Zhang, Chunqiu Fan, Luyao Wang, Taoran Li, Min Wang, Ying Han, Jiehui Jiang, Alzheimer’S Disease Neuroimaging Initiative

Faculty, Staff and Student Publications

Amyloid-β (Aβ) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aβ positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in …

Leptin Reduction As A Required Component For Weight Loss, Shangang Zhao, Na Li, Wei Xiong, Guannan Li, Sijia He, Zhuzhen Zhang, Qingzhang Zhu, Nisi Jiang, Christian Ikejiofor, Yi Zhu, May-Yun Wang, Xianlin Han, Ningyang Zhang, Carolina Solis-Herrera, Christine Kusminski, Zhiqiang An, Joel K Elmquist, Philipp E Scherer

Faculty, Staff and Students Publications

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or …

Gad65abs Are Not Associated With Beta-Cell Dysfunction In Patients With T2d In The Grade Study, Christiane S Hampe, Ali Shojaie, Barbara Brooks-Worrell, Sepideh Dibay, Kristina Utzschneider, Steven E Kahn, Mary E Larkin, Mary L Johnson, Naji Younes, Neda Rasouli, Cyrus Desouza, Robert M Cohen, Jean Y Park, Hermes J Florez, Willy Marcos Valencia, Robert Stempel, Jerry P Palmer, Ashok Balasubramanyam

Faculty, Staff and Students Publications

CONTEXT: Autoantibodies directed against the 65-kilodalton isoform of glutamic acid decarboxylase (GAD65Abs) are markers of autoimmune type 1 diabetes (T1D) but are also present in patients with Latent Autoimmune Diabetes of Adults and autoimmune neuromuscular diseases, and also in healthy individuals. Phenotypic differences between these conditions are reflected in epitope-specific GAD65Abs and anti-idiotypic antibodies (anti-Id) against GAD65Abs. We previously reported that 7.8% of T2D patients in the GRADE study have GAD65Abs but found that GAD65Ab positivity was not correlated with beta-cell function, glycated hemoglobin (HbA1c), or fasting glucose levels.

CONTEXT: In this study, we aimed to better characterize islet autoantibodies …

Regional Variability In The Prevalence Of Food Insecurity And Diet Quality Among United States Children, Jayna M Dave, Tzuan A Chen, Alexandra N Castro, Mamie White, Elizabeth A Onugha, Sloane Zimmerman, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Understanding the association between food security status (FSS) and diet quality in children is crucial. This study investigated regional variability in FSS, participation in the federal nutrition assistance program (FNAP), and diet quality among US children. National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2016 were analyzed. The association between FSS, FNAP participation, and diet quality (Healthy Eating Index—HEI-2015) was assessed using multiple linear/logistic regression models. The sample included 6403 children (mean age: 7.5 years; 51% male; 33% Hispanic). Within the sample, 13% reported child food insecurity, and 30% reported household food insecurity. Additionally, 90% participated in …

Effects Of Food Bar Chewing Duration On The Physiologic, Metabolic, And Perceptual Responses To Moderate-Intensity Running, Thomas R. Geaney, Zachary A. Sievert, J. David Branch, Patrick B. Wilson

Exercise Science Faculty Publications

Purpose

Chewing duration can affect food particle size, gastric processing, and postprandial glycemia, but these effects have not been investigated with exercise. This study examined how the chewing duration of a food bar impacts glycemic and metabolic responses, gastrointestinal (GI) symptoms, psychological affect, and performance during endurance running.

Methods

This randomized, unblinded, crossover study had 15 males (35.2 ± 7.4 years, VO_2peak: 56.1 ± 5.2 ml/kg/min) attend three laboratory visits. Visit 1 required a VO_2peak test, 10 min familiarization run at 60% VO2peak, and familiarization time-to-exhaustion (TTE) test (10 min at 90% VO_2peak, followed by …

Adjusting For Covariates Representing Potential Confounders, Mediators, Or Competing Predictors In The Presence Of Measurement Error: Dispelling A Potential Misapprehension And Insights For Optimal Study Design With Nutritional Epidemiology Examples, Roger S Zoh, Diana M Thomas, Carmen D Tekwe, Xiaoxin Yu, Colby J Vorland, Nikhil V Dhurandhar, David M Klurfeld, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Variables such as dietary intake are measured with error yet frequently used in observational epidemiology. Although this limitation is sometimes noted, these variables are still often modeled as covariates without formal correction or sincere dialogue about measurement unreliability potentially weakening the validity of statistical conclusions. Further, larger sample sizes increase power (bias) to detect spurious correlations. Counterintuitively, recent work suggested a non-monotonic relationship between confounder unreliability and how much controlling for the confounder reduces (or induces) bias when testing for an exposure-outcome association. If true, such non-monotonicity would be especially concerning for applications such as nutrition, where measurement reliability …

Catalyzing Communities Of Research Rigour Champions, Audrey C Brumback, William X Q Ngiam, Dana M Lapato, David B Allison, Christin L Daniels, Michael Dougherty, Haley F Hazlett, Kara L Kerr, Susan Pusek, Naomi Schrag

Children’s Nutrition Research Center Staff Publications

The biomedical sciences must maintain and enhance a research culture that prioritizes rigour and transparency. The US National Institute of Neurological Disorders and Stroke convened a workshop entitled 'Catalyzing Communities of Research Rigor Champions' that brought together a diverse group of leaders in promoting research rigour and transparency (identified as 'rigour champions') to discuss strategies, barriers and resources for catalyzing technical, cultural and educational changes in the biomedical sciences. This article summarizes 2 days of panels and discussions and provides an overview of critical barriers to research rigour, perspectives behind reform initiatives and considerations for stakeholders across science. Additionally, we …

Objective Assessment Of Shared Plate Eating Using A Wearable Camera In Urban And Rural Households In Ghana, Christabel A Domfe, Megan A Mccrory, Edward Sazonov, Tonmoy Ghosh, Viprav Raju, Gary Frost, Matilda Steiner-Asiedu, Mingui Sun, Wenyan Jia, Tom Baranowski, Benny Lo, Alex K Anderson

Children’s Nutrition Research Center Staff Publications

Background: Shared plate eating (SPE), defined as two or more individuals eating directly from the same plate or bowl, is a common household food consumption practice in many Low- and Middle-Income Countries (LMICs). Examination of household engagement in SPE remains largely unexplored, highlighting a gap in research when interpreting dietary information obtained from these settings. The dearth of research into SPE can be attributed to the inherent limitations of traditional dietary assessment methods which constrain their usability in settings where SPE is common.

Objective: In this expository narrative, we describe what SPE is when it is practiced in an LMIC …

Novel, Pathogenic Insertion Variant Of Gsdme Associates With Autosomal Dominant Hearing Loss In A Large Chinese Pedigree, Jingliang Cheng, Ting Li, Qi Tan, Jiewen Fu, Lianmei Zhang, Luquan Yang, Baixu Zhou, Lisha Yang, Shangyi Fu, Alora Grace Linehan, Junjiang Fu

Children’s Nutrition Research Center Staff Publications

Nonsyndromic hearing loss (NSHL) is a genetically diverse, highly heterogeneous condition characterised by deafness, and Gasdermin E (GSDME) variants have been identified as directly inducing autosomal dominant NSHL. While many NSHL cases associated with GSDME involve the skipping of exon 8, there is another, less understood pathogenic insertion variant specifically found in Chinese pedigrees that causes deafness, known as autosomal dominant 5 (DFNA5) hearing loss. In this study, we recruited a large Chinese pedigree, conducted whole‐exome and Sanger sequencing to serve as a comprehensive clinical examination, and extracted genomic DNA samples for co‐segregation analysis of the members. Conservation …

Combinatorial Atoh1, Gfi1, Pou4f3, And Six1 Gene Transfer Induces Hair Cell Regeneration In The Flat Epithelium Of Mature Guinea Pigs, Yujie Liu, Lin Yang, Sunita Singh, Lisa A Beyer, Diane M Prieskorn, Donald L Swiderski, Andrew K Groves, Yehoash Raphael

Children’s Nutrition Research Center Staff Publications

Flat epithelium (FE) is a condition characterized by the loss of both hair cells (HCs) and supporting cells and the transformation of the organ of Corti into a simple flat or cuboidal epithelium, which can occur after severe cochlear insults. The transcription factors Gfi1, Atoh1, Pou4f3, and Six1 (GAPS) play key roles in HC differentiation and survival in normal ears. Previous work using a single transcription factor, Atoh1, to induce HC regeneration in mature ears in vivo usually produced very few cells and failed to produce HCs in severely damaged organs of Corti, especially those with FE. Studies in vitro …

A Comprehensive Review Of Advances In Hepatocyte Microencapsulation: Selecting Materials And Preserving Cell Viability, Hailian Wang, Lebin Wen, Fengdi Jiang, Pengyu Ren, Yixin Yang, Siyuan Song, Zhengteng Yang, Yi Wang

Children’s Nutrition Research Center Staff Publications

Liver failure represents a critical medical condition with a traditionally grim prognosis, where treatment options have been notably limited. Historically, liver transplantation has stood as the sole definitive cure, yet the stark disparity between the limited availability of liver donations and the high demand for such organs has significantly hampered its feasibility. This discrepancy has necessitated the exploration of hepatocyte transplantation as a temporary, supportive intervention. In light of this, our review delves into the burgeoning field of hepatocyte transplantation, with a focus on the latest advancements in maintaining hepatocyte function, co-microencapsulation techniques, xenogeneic hepatocyte transplantation, and the selection of …

Advancing Kidney Xenotransplantation With Anesthesia And Surgery – Bridging Preclinical And Clinical Frontiers Challenges And Prospects, Xiaojian Zhang, Hailian Wang, Qin Xie, Yang Zhang, Yixin Yang, Man Yuan, Yuqi Cui, Si-Yuan Song, Jianzhen Lv, Yi Wang

Children’s Nutrition Research Center Staff Publications

Xenotransplantation is emerging as a vital solution to the critical shortage of organs available for transplantation, significantly propelled by advancements in genetic engineering and the development of sophisticated immunosuppressive treatments. Specifically, the transplantation of kidneys from genetically engineered pigs into human patients has made significant progress, offering a potential clinical solution to the shortage of human kidney supply. Recent trials involving the transplantation of these modified porcine kidneys into deceased human bodies have underscored the practicality of this approach, advancing the field towards potential clinical applications. However, numerous challenges remain, especially in the domains of identifying suitable donor-recipient matches and …

Promoting Trustworthiness Of Science: Reproducing And Verifying Agarwal Et Al's (2022) Findings Through Collaborative Endeavors, Yasaman Jamshidi-Naeini, Nicolas Escobar Velasquez, Lilian Golzarri-Arroyo, Sumayyah Ali, Luke R Howard, Stephanie Dickinson, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Liver Directed Adeno-Associated Viral Vectors To Treat Metabolic Disease, Marcel A Chuecos, William R Lagor

Faculty, Staff and Students Publications

The liver is the metabolic center of the body and an ideal target for gene therapy of inherited metabolic disorders (IMDs). Adeno-associated viral (AAV) vectors can deliver transgenes to the liver with high efficiency and specificity and a favorable safety profile. Recombinant AAV vectors contain only the transgene cassette, and their payload is converted to non-integrating circular double-stranded DNA episomes, which can provide stable expression from months to years. Insights from cellular studies and preclinical animal models have provided valuable information about AAV capsid serotypes with a high liver tropism. These vectors have been applied successfully in the clinic, particularly …

The Impact Of Obesity-Associated Glycine Deficiency On The Elimination Of Endogenous And Exogenous Metabolites Via The Glycine Conjugation Pathway, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: Glycine is an integral component of the human detoxification system as it reacts with potentially toxic exogenous and endogenously produced compounds and metabolites via the glycine conjugation pathway for urinary excretion. Because individuals with obesity have reduced glycine availability, this detoxification pathway may be compromised. However, it should be restored after bariatric surgery because of increased glycine production.

OBJECTIVE: To examine the impact of obesity-associated glycine deficiency on the glycine conjugation pathway. We hypothesize that the synthesis rates of acylglycines from endogenous and exogenous sources are significantly reduced in individuals with obesity but increase after bariatric surgery.

METHODS: We …

Effects And Plasma Proteomic Analysis Of Glp-1ra Versus Cpa/Ee, In Combination With Metformin, On Overweight Pcos Women: A Randomized Controlled Trial, Mingyu Liao, Xing Li, Hao Zhang, Ling Zhou, Liu Shi, Weixin Li, Rufei Shen, Guiliang Peng, Huan Zhao, Jiaqing Shao, Xiujie Wang, Zheng Sun, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

PURPOSE: Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus cyproterone acetate/ethinylestradiol (CPA/EE) + Met in overweight PCOS women and identify potential proteomic biomarkers of disease risk in women with PCOS.

METHODS: In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day: 2 mg cyproterone acetate and 35-μg ethinylestradiol,) +Met (1500 mg/day) or GLP-1 RA (liraglutide, 1.2-1.8 mg/day) +Met (1500 mg/day) for 12 weeks. …

Investigation Of Setmelanotide, An Mc4r Agonist, For Obesity In Individuals With Smith-Magenis Syndrome, Julia Lazareva, Stephanie R Sisley, Sheila M Brady, Ann C M Smith, Sarah H Elsea, Jeremy J Pomeroy, Christian L Roth, Jennifer E Sprague, Martin Wabitsch, Jill Garrison, Jack A Yanovski

Children’s Nutrition Research Center Staff Publications

Background: Smith Magenis Syndrome (SMS) is a rare genetic disorder caused by RAI1 haploinsufficiency. Obesity in people with SMS is believed partially due to dysfunction of the proximal melanocortin 4 receptor (MC4R) pathway. We therefore studied effects of treatment with the MC4R agonist setmelanotide on obesity and hunger, as well as metabolic, cardiac and safety, in individuals with SMS.

Methods: People with SMS received once-daily setmelanotide injections, with the dose titrated bi-weekly to a maximum of 3 mg over ∼1 month; and a full-dose treatment duration of 3mo. The primary outcome was percent change in body weight. Secondary outcomes included …

Adipose Tissue Lymphocytes And Obesity, Feng Gao, Benjamin Litchfield, Huaizhu Wu

Faculty, Staff and Students Publications

Obesity is associated with chronic inflammation in adipose tissue (AT), mainly evidenced by infiltration and phenotypic changes of various types of immune cells. Macrophages are the major innate immune cells and represent the predominant immune cell population within AT. Lymphocytes, including T cells and B cells, are adaptive immune cells and constitute another important immune cell population in AT. In obesity, CD8+ effector memory T cells, CD4+ Th1 cells, and B2 cells are increased in AT and promote AT inflammation, while regulatory T cells and Th2 cells, which usually function as immune regulatory or type 2 inflammatory cells, are reduced …

Cardiovascular Risk Factors In Sheehan's Syndrome: A Case-Control Study, Mayur Agrawal, Subhash C Yadav, Swish K Singh, Sheo Kumar, Krishnarpan Chatterjee, Naveen K Garg

Faculty, Staff and Student Publications

INTRODUCTION: Obesity, dyslipidaemia and insulin resistance are associated with hypopituitarism. The association between these conditions and Sheehan's syndrome (SS) caused by post-partum pituitary gland necrosis is poorly understood. This study aimed to assess cardiovascular risk surrogate markers in SS patients, and we compared clinical, biochemical and radiological testing with healthy controls.

METHODS: In this cross-sectional study, we studied 45 patients with SS on standard replacement therapy and compared them with healthy controls. All subjects underwent anthropometric, inflammatory marker and hormonal measurement (adrenocorticotropic hormone (ACTH), stimulated cortisol, insulin-like growth factor-1 (IGF-1), thyroxine (T4), follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol (E2), …

Variant Of The Lactase Lct Gene Explains Association Between Milk Intake And Incident Type 2 Diabetes, Kai Luo, Guo-Chong Chen, Yanbo Zhang, Jee-Young Moon, Jiaqian Xing, Brandilyn A Peters, Mykhaylo Usyk, Zheng Wang, Gang Hu, Jun Li, Elizabeth Selvin, Casey M Rebholz, Tao Wang, Carmen R Isasi, Bing Yu, Rob Knight, Eric Boerwinkle, Robert D Burk, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Cow's milk is frequently included in the human diet, but the relationship between milk intake and type 2 diabetes (T2D) remains controversial. Here, using data from the Hispanic Community Health Study/Study of Latinos, we show that in both sexes, higher milk intake is associated with lower risk of T2D in lactase non-persistent (LNP) individuals (determined by a variant of the lactase LCT gene, single nucleotide polymorphism rs4988235 ) but not in lactase persistent individuals. We validate this finding in the UK Biobank. Further analyses reveal that among LNP individuals, higher milk intake is associated with alterations in gut microbiota (for …

Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia

Journal of Nonprofit Innovation

Urban farming can enhance the lives of communities and help reduce food scarcity. This paper presents a conceptual prototype of an efficient urban farming community that can be scaled for a single apartment building or an entire community across all global geoeconomics regions, including densely populated cities and rural, developing towns and communities. When deployed in coordination with smart crop choices, local farm support, and efficient transportation then the result isn’t just sustainability, but also increasing fresh produce accessibility, optimizing nutritional value, eliminating the use of ‘forever chemicals’, reducing transportation costs, and fostering global environmental benefits.

Imagine Doris, who is …

Glp1 Receptor Agonists-Effects Beyond Obesity And Diabetes, Sydney S Wilbon, Mikhail G Kolonin

Faculty, Staff and Student Publications

Glucagon-like peptide-1 receptor agonists (GLP1RA) have been transformative for patients and clinicians in treating type-2 diabetes and obesity. Drugs of this class, the bioavailability of which is continuously improving, enable weight loss and control blood glucose with minimal unwanted side effects. Since adopting GLP1RA for treating metabolic diseases, animal and clinical studies have revealed their beneficial effects on several other pathologies, including cardiovascular diseases, neurodegeneration, kidney disease, and cancer. A notable commonality between these diseases is their association with older age. Clinical trials and preclinical data suggest that GLP1RA may improve outcomes in these aging-related diseases. Some of the benefits …

Leptin Decreases Gluconeogenesis And Gluconeogenic Substrate Availability In Patients With Lipodystrophy, Emmanuel Quaye, Shaji Chacko, Megan Startzell, Rebecca J Brown

Children’s Nutrition Research Center Staff Publications

Context: The effects of leptin, an adipocyte-derived hormone that signals overall energy sufficiency, can only be studied in leptin-deficient conditions. In patients with lipodystrophy, a rare disease and unique model of leptin deficiency, treatment with recombinant leptin (metreleptin) improves glycemia and decreases energy expenditure. We hypothesized that these improvements might be mediated by reduced gluconeogenesis (GNG), an energy-requiring process.

Objective: To determine the effects of metreleptin on GNG and GNG substrates.

Methods: This was a single-arm prospective study of metreleptin administration in 15 patients with lipodystrophy, 9 of whom had data on GNG (NIH, 2013-2018). We analyzed total GNG, insulin-mediated …

Ints6 And The Integrator Phosphatase Module Tune The Efficiency Of Select Premature Transcription Termination Events, Rina Fujiwara, Si-Nan Zhai, Dongming Liang, Aayushi P Shah, Matthew Tracey, Xu-Kai Ma, Christopher J Fields, María Saraí Mendoza-Figueroa, Michele C Meline, Deirdre C Tatomer, Li Yang, Jeremy E Wilusz

Children’s Nutrition Research Center Staff Publications

The metazoan-specific Integrator complex catalyzes 3' end processing of small nuclear RNAs (snRNAs) and premature termination that attenuates the transcription of many protein-coding genes. Integrator has RNA endonuclease and protein phosphatase activities, but it remains unclear if both are required for complex function. Here, we show IntS6 (Integrator subunit 6) over-expression blocks Integrator function at a subset of Drosophila protein-coding genes, although having no effect on snRNAs or attenuation of other loci. Over-expressed IntS6 titrates protein phosphatase 2A (PP2A) subunits, thereby only affecting gene loci where phosphatase activity is necessary for Integrator function. IntS6 functions analogous to a PP2A regulatory …