Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Skin Carotenoid Scores Are A Valid Approximation Of Fruit And Vegetable Intake Among Adults With Obesity, Stephanie B Jilcott Pitts, Qiang Wu, Elizabeth Gates, Melissa N Laska, Andrew R Dinardo, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Skin carotenoid score (SCS) as measured using pressure-mediated reflection spectroscopy has been validated among adults with normal and overweight body mass index, with little validation research among adults with obesity. Therefore, the purpose of this exploratory study was to examine the validity of SCS as an approximation of fruit and vegetable intake among adults with obesity. We used samples from adults with obesity from three prior studies: The first study examined the validity of SCS among 213 adults, 34 with obesity; the second, examined sensitivity of SCS to a β-carotene-rich juice intervention among 162 adults, 14 with obesity; the third …

Non-Enzymatic Hepatic Abhd6 Interacts With Akt-Foxo1 Axis To Regulate Metabolic Health, Guannan Li, Laurence T Maeyens, Jiyuan Yin, Jan-Bernd Funcke, Chanmin Joung, Ruizhen Li, Ziying Xu, Ting Wu, Xin Li, Nisi Jiang, Mbolle Ekane, Maria Paula Lopez, Pengju Cao, Sijia He, Adam B Salmon, S R Murthy Madiraju, Marc Prentki, Juli Bai, James F Nelson, Xianlin Han, Yi Zhu, Shangang Zhao

Children’s Nutrition Research Center Staff Publications

The enzymatic role of ABHD6 in insulin secretion and resistance is well documented. However, its non-enzymatic function, especially its effects on metabolic health, including selective hepatic insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD), is poorly understood. To define the role of ABHD6 in liver physiology, we generated liver-specific ABHD6 knockout mice, as well as liver-specific native and enzymatically inactive mutant ABHD6 overexpression mouse models. We demonstrate that non-enzymatic ABHD6 contributes to the regulation of selective hepatic insulin resistance and MASLD progression. Mechanistically, we show that ABHD6 localizes to the nucleus and interacts with Akt/FoxO1 axis to regulate insulin …

Community Participatory Co-Design And Development Of A Digital Diabetes Prevention Education Program For Hispanic Families With Obesity: Mixed Methods Study, Sandra Mihail, Marbelly Partida, Lizette Villanueva, Debbe Thompson, Teresia M O'Connor, Salma M Musaad, Maria J Redondo, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Background: Digital health interventions (DHIs) can extend the reach of disease prevention interventions; however, few are evidence-based, theoretically grounded, or developed for high-risk youth and families. Co-design approaches engage end users in the design and development of the DHI, which can lead to increased accessibility and engagement.

Objective: This study aimed to describe the adaptation of an evidence-based diabetes prevention program for remote, digital delivery.

Methods: The adaptation of the in-person intervention was guided by a modified Inclusive Digital Health Intervention Design to Promote Health Equity framework and conducted in collaboration with Hispanic adolescents (n=23) with obesity (BMI ≥95th percentile) …

Bariatric Surgery Impacts Immune Cell Metabolism And Function Dependent On Metabolic Status, Samantha N. Hart

University of Kentucky Doctoral Dissertations

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with …

The Impact Of Gastric Sleeve And Roux-En-Y Gastric Bypass On Chief Cell Function And Protein Digestion In Obese Patients, Garikoitz Mikel Gainza

Honors Undergraduate Theses

Obesity has become one of the largest global health concerns of the 21^st century, correlating with numerous associated diseases. To help address the growing prevalence and burden of obesity, sleeve gastrectomy and Roux-en-Y gastric bypass have become two commonly performed surgical procedures done to promote weight loss by altering the anatomical structure of the stomach and surrounding organs of the gastrointestinal system. Although the benefits of improved metabolism linked to these surgical procedures are well studied, their impact on the physiology of gastric cells, and more specifically chief cells as they relate to protein digestion post-surgery, is yet to …

The Treatment Of Obesity In The Context Of The Obesity Paradox In Patients With Heart Failure: A Narrative Review, Pamela L. Alebna, Sarah Martey, Anurag Mehta, Carl J. Lavie, Salvatore Carbone

EVMS School of Health Professions Faculty Publications

Purpose of review

While excess adiposity is a known risk factor for incident heart failure ( HF), once the condition is established, observational data suggest that increased body mass index (BMI) may confer a survival advantage. This paradox has emphasized the underlying roles of cardiorespiratory fitness (CRF), and body composition, particularly lean mass (LM), in influencing clinical outcomes.

Recent findings

In this review, we explore the multifaceted nature of the obesity paradox in HF, with a focus on emerging anti-obesity incretin-mimetic therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. These agents …

A Cross-Sectional Study Investigating The Relationship Between The Fto Gene Polymorphism In Relation To Obesity Traits And Vitamin D Status In Adolescence, Ahmad Al-Serri, Rabeah A. Al-Temaimi, Abdullah Al-Taiar, Lemia Shaban, Reem Al-Sabah, Abdur Rahman, Ali H. Ziyab

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Background and Objective: Obesity affects 18%-25% of adolescents globally and represents a major public health challenge. Genetic factors contribute to obesity susceptibility, with the FTO gene variant rs9939609 consistently associated with obesity in adults; however, evidence in adolescents is limited. This study examined the association between FTO and obesity traits in adolescents and explored potential interactions with vitamin D status.

Methods: In this cross-sectional study, 509 adolescents aged 10-15 years were genotyped for FTO rs9939609. Obesity traits, including BMI, BMI z-score, and waist circumference, were assessed. Associations with genotype were analyzed using an additive genetic model, and potential interactions with …

Vitamin D Status During Pregnancy Modulates The Effect Of Pre-Pregnancy Obesity On Gestational Diabetes Mellitus Risk: A Birth Cohort Study, Ali H. Ziyab, Abdullah Al-Taiar, Reem Al-Sabah, Majeda S. Hammoud, Saeed Akhtar

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Objective:

To determine whether gestational vitamin D status modulates the effect of pre-pregnancy obesity on gestational diabetes mellitus (GDM) risk while stratifying by maternal age.

Design:

Birth cohort.

Setting:

A major maternity hospital in Kuwait.

Participants:

Pregnant women in their second/third trimester of gestation were enrolled. Pre-pregnancy body mass index (BMI, kg/m²) was categorized as under/normal weight (< 25.0), overweight (25.0 to < 30.0), and obesity (≥30.0). Gestational 25-hydroxyvitamin D concentrations were categorized as deficiency (< 50 nmol/L) or insufficiency/sufficiency (≥50 nmol/L). GDM status was ascertained according to international guidelines. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using logistic regression.

Results:

Data from 957 pregnant women were analyzed, with GDM affecting 166 (17.4%) pregnancies. Pre-pregnancy obesity and gestational vitamin D deficiency was ascertained in 275 (28.7%) and 533 (55.7%) pregnant women, respectively. The association between pre-pregnancy obesity and GDM risk differed according …

Repeated Withdrawal Of A Glpr Agonist Induces Hyperleptinemia And Deteriorates Metabolic Health In Obese Aging Um-Het3 Mice, Nisi Jiang, Jiyuan Yin, Noah Lawrence, Jieyi Meng, Laurence T Maeyens, Ziying Xu, Xin Li, Mbolle Ekane, Ariana Chaudhary, Pengju Cao, Guannan Li, Carolina Solis-Herrera, Yi Zhu, Shangang Zhao

Children’s Nutrition Research Center Staff Publications

GLP-1-based therapy is highly effective in combating aging-associated metabolic diseases. However, the metabolic effects of frequent withdrawal from this therapy in aged, obese mice have not been previously studied. In this study, aged obese UM-HET3 mice were assigned to three groups: Group 1 received no liraglutide treatment (Lira OFF); Group 2 underwent 3 cycles of treatment followed by withdrawal (Lira ON/OFF); and Group 3 remained on continuous treatment (Lira ON). As expected, mice in Group 3 showed reduced body weight and food intake, along with improved metabolic health. In contrast, mice in Group 2 developed hyperleptinemia and visceral fat expansion, …

Multicenter Span Trial Of Fasudil In Ischemic Stroke, Takahiko Imai, Andreia Lopes De Morais, Xuyan Jin, Tao Qin, Jessica Lamb, Karisma A Nagarkatti, Mu-Hsun Chen, Ligia S B Boisserand, Rakesh B Patel, Mariia Kumskova, Anjali Chauhan, Krishnan M Dhandapani, Mohammad B Khan, Pradip K Kamat, Yanrong Shi, Suyi Cao, Basavaraju G Sanganahalli, Joseph B Mandeville, Patrick D Lyden, David C Hess, Enrique C Leira, Anil K Chauhan, Jaroslaw Aronowski, Louise D Mccullough, Raymond C Koehler, Lauren H Sansing, Márcio A Diniz, Cenk Ayata

Children’s Nutrition Research Center Staff Publications

Background: The SPAN (Stroke Preclinical Assessment Network) is a confirmatory multicenter trial network to test cerebroprotective interventions in experimental acute stroke. In a first-of-its-kind trial, SPAN tested 6 interventions in a rodent model of transient focal ischemic stroke. Here, we report the efficacy of fasudil, an isoform-nonselective rho-associated kinase inhibitor, on primary and secondary outcomes in the SPAN trial.

Methods: Fasudil was administered at 10 mg/kg intraperitoneally every 12 hours for 6 doses starting 5 minutes before reperfusion in a 60-minute endovascular filament middle cerebral artery occlusion model. The active treatment arm (n=345) was compared with the pooled intraperitoneal and …

Family-Level Factors That Influence Physical Activity Among Hispanic Adolescents At Risk For Type 2 Diabetes, Sandra Mihail, Ayleen A Hernandez, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Objective: Family-based health promotion and disease prevention strategies are recommended as best practice; however, there is limited knowledge regarding the family-level factors that influence modifiable behavior risk factors like physical activity (PA) among Latinx adolescents. This study addressed this knowledge gap by using qualitative methods to identify perceptions of family-level factors that influence PA among Hispanic youth.

Methods: We conducted semistructured, open-ended interviews with 20 Latinx adolescents (14-16 years) with obesity (body mass index ≥95th percentile) to identify their perceptions of how family influences PA. Content analysis was used to identify emergent themes, which were then compared across demographic factors, …

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 …

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 …

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 …

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 …

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/.

“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.

Mesoderm-Specific Transcript Has A Role In The Systemic Regulation Of Obesity, Maria J. Orellana Rosales

Thinking Matters Symposium

Mesoderm specific transcript (Mest) expression in white adipose tissue (WAT) is variable in genetically identical mice. Previous studies have shown a connection between Mest high expression and propensity for fat mass expansion. WAT and liver crosstalk has been well documented with hormone-like peptides signaling and regulating important metabolic pathways. The aim of this study is to investigate the correlation between these circulating factors and Mest expression in mice after exposure to a high fat diet (HFD). A group of 120 C57B6/J mice, males and females, were exposed to a HFD (Western Diet, 40 kcal% fat) for 4 weeks (8-12 weeks …

Exploring The Acute Effects Of Sedentary Behaviors On Cardiometabolic Risk In Hispanic Adolescents With Obesity: A Randomized Crossover Study, Erica G Soltero, Osamah Salim, Yiming Mirabile, Salma M Musaad

Children’s Nutrition Research Center Staff Publications

Background/Objectives: Time spent in sedentary pursuits is associated with adverse metabolic profiles. Adolescents spend 65-75% of their day in sedentary pursuits; however, evidence among youth is less conclusive. This study examined the effects of an acute 4 h bout of sedentary behaviors on cardiometabolic outcomes and energy expenditure in Hispanic adolescents (12-16 years old) with obesity (BMI% ≥ 95th).

Methods: This study used a randomized cross-over design to engage participants (N = 12) in two sedentary conditions, an active condition where youth were engaged in two hours of 'active' sitting activities (e.g., reading and puzzles) and two hours …

Vestibular Neurons Link Motion Sickness, Behavioural Thermoregulation And Metabolic Balance In Mice, Longlong Tu, Xing Fang, Yongjie Yang, Meng Yu, Hailan Liu, Hesong Liu, Na Yin, Jonathan C Bean, Kristine M Conde, Mengjie Wang, Yongxiang Li, Olivia Z Ginnard, Qingzhuo Liu, Yuhan Shi, Junying Han, Yi Zhu, Makoto Fukuda, Qingchun Tong, Benjamin Arenkiel, Mingshan Xue, Yang He, Chunmei Wang, Yong Xu

Children’s Nutrition Research Center Staff Publications

Motion sickness is associated with thermoregulation and metabolic control, but the underlying neural circuitry remains largely unknown. Here we show that neurons in the medial vestibular nuclei parvocellular part (MVePC) mediate the hypothermic responses induced by motion. Reactivation of motion-sensitive MVePC neurons recapitulates motion sickness in mice. We show that motion-activated neurons in the MVePC are glutamatergic (MVePCGlu), and that optogenetic stimulation of MVePCGlu neurons mimics motion-induced hypothermia by signalling to the lateral parabrachial nucleus (LPBN). Acute inhibition of MVePC-LPBN circuitry abrogates motion-induced hypothermia. Finally, we show that chronic inhibition of MVePCGlu neurons prevents diet-induced obesity and improves glucose homeostasis …

Gastroesophageal Reflux And Gastrointestinal Symptoms After Metabolic And Bariatric Surgery In Adolescents: An 8-Year Follow-Up Analysis, John B Rode, Suhail A Zeineddin, Jane C Khoury, Todd M Jenkins, Stephanie R Sisley, Anita P Courcoulas, Justin R Ryder, Marc P Michalsky, Thomas H Inge

Children’s Nutrition Research Center Staff Publications

Importance: Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed metabolic and bariatric surgery (MBS) procedures in adolescents and adults. Despite their safety and effectiveness, there is concern over postoperative gastrointestinal symptoms (GIS), especially gastroesophageal reflux symptoms (GERS), in those undergoing VSG.

Objective: To evaluate the long-term prevalence of GIS in adolescents who underwent RYGB or VSG.

Design, setting, and participants: This is a prospective, multicenter, observational cohort study at five academic referral centers in the United States. Patients were enrolled from February 28, 2007, through December 30, 2011. The analysis included 228 adolescents: 161 …

Adipose Progenitor Cell-Derived Extracellular Vesicles Suppress Macrophage M1 Program To Alleviate Midlife Obesity, Qing Zhou, Jia Gao, Guorao Wu, Chenwei Wang, Yan Yang, Teng Huang, Yi Wang, Tiantian Yue, Zhichao Gao, Hao Xie, Fei Xiong, Ke Xiang, Tuying Yong, Wanguang Zhang, Tongtong Zhang, Wen Kong, Cai Chen, Shu Zhang, Qilin Yu, Xuemei Fan, Shiwei Liu, Yanjun Liu, Cong-Yi Wang

Children’s Nutrition Research Center Staff Publications

Among different age groups, middle-aged individuals are particularly susceptible to obesity, with a 22% higher risk of all-cause mortality. However, the underlying mechanisms remain unclear. In this study, we identify adipose progenitor cells (APCs) in the white adipose tissue (WAT) of middle-aged subjects as potential causes of midlife obesity. Specifically, the extracellular vesicles (EVs) derived from APCs display an impaired ability to mitigate the inflammaging of adipose tissue macrophages (ATMs) in middle-aged individuals. Mechanistically, these EVs, lacking miR-145-5p, fail to suppress the expression of L-selectin in ATMs, thereby facilitating their M1 program via the NF-κB signaling pathway. In contrast, EVs …

Insulin Clearance At Randomisation And In Response To Treatment In Youth With Type 2 Diabetes: A Secondary Analysis Of The Today Randomised Clinical Trial, Kristen J Nadeau, Silva A Arslanian, Fida Bacha, Sonia Caprio, Lily C Chao, Ryan Farrell, Kara S Hughan, Maria Rayas, Melinda Tung, Kaitlyn Cross, Laure El Ghormli

Children’s Nutrition Research Center Staff Publications

Aims/hypothesis: Insulin resistance and compensatory hyperinsulinaemia are core features leading to beta cell failure in youth-onset type 2 diabetes. Insulin clearance (IC) is also a key regulator of insulin concentrations, but few data exist on IC in youth-onset type 2 diabetes. In a secondary analysis of our Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomised clinical trial, we investigated potential sex-, race-, ethnicity- and treatment-related differences in IC in youth-onset type 2 diabetes and aimed to identify metabolic phenotypes associated with IC at baseline and in response to metformin, metformin plus a lifestyle intervention, and metformin …

A Β-Hydroxybutyrate Shunt Pathway Generates Anti-Obesity Ketone Metabolites, Maria Dolores Moya-Garzon, Mengjie Wang, Veronica L Li, Xuchao Lyu, Wei Wei, Alan Sheng-Hwa Tung, Steffen H Raun, Meng Zhao, Laetitia Coassolo, Hashim Islam, Barbara Oliveira, Yuqin Dai, Jan Spaas, Antonio Delgado-Gonzalez, Kenyi Donoso, Aurora Alvarez-Buylla, Francisco Franco-Montalban, Anudari Letian, Catherine P Ward, Lichao Liu, Katrin J Svensson, Emily L Goldberg, Christopher D Gardner, Jonathan P Little, Steven M Banik, Yong Xu, Jonathan Z Long

Children’s Nutrition Research Center Staff Publications

β-Hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve the interconversion of BHB and primary energy intermediates. Here, we identify a previously undescribed BHB secondary metabolic pathway via CNDP2-dependent enzymatic conjugation of BHB and free amino acids. This BHB shunt pathway generates a family of anti-obesity ketone metabolites, the BHB-amino acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid BHB-ylation activity and reduces BHB-amino acid levels. The most abundant BHB-amino acid, BHB-Phe, is a ketosis-inducible congener of Lac-Phe that activates hypothalamic and brainstem neurons and suppresses feeding. Conversely, CNDP2-KO mice exhibit …

Commentary: Impact Of Resistance Training Intensity On Body Composition And Nutritional Intake Among College Women With Overweight And Obesity: A Cluster Randomized Controlled Trial, Joshua L Keller, Sarah E Deemer, Gian Luca Di Tanna, Sherri L Pals, Kevin R Fontaine, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Sex-Specific Roles Of The Adipocyte Mineralocorticoid Receptor In Obesity And Early Life Stress, Meghan B. Turner

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a burgeoning health epidemic caused by chronic overnutrition and exacerbated by genetic, environmental and developmental factors. The adipocyte mineralocorticoid receptor (MR), a transcriptionally active nuclear receptor, is speculated to contribute to metabolic dysfunction in the obese state. MR expression is increased in obese adipose tissue, and MR modulates the expression of fat-derived hormones such as leptin and adiponectin. In women, obesity can be exacerbated by early life stress, such as adverse childhood experiences (ACEs). Studies show that women display a positive association between cumulative ACE exposures and increased body mass index. Previously, we demonstrated that maternal separation and …

Key Brain Region Identification In Obesity Prediction With Structural Mri And Probabilistic Uncertainty Aware Model, Walia Farzana, Megan A. Witherow, Ahmed Temtam, Liangsuo Ma, Melanie Bean, F. Gerry Moeller, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Objectives/Goals: Predictive performance alone may not determine a model’s clinical utility. Neurobiological changes in obesity alter brain structures, but traditional voxel-based morphometry is limited to group-level analysis. We propose a probabilistic model with uncertainty heatmaps to improve interpretability and personalized prediction. Methods/Study Population: The data for this study are sourced from the Human Connectome Project (HCP), with approval from the Washington University in St. Louis Institutional Review Board. We preprocessed raw T1-weighted structural MRI scans from 525 patients using an automated pipeline. The dataset is divided into training (357 cases), calibration (63 cases), and testing (105 cases). Our probabilistic model …

Obesity Prediction From Structural Mri Using Conformal Deep Learning With Uncertainty Quantification, W. Farzana, A. G. A. Temtam, B. Humud-Arboleda, L. Ma, M. Bean, F. Gerard Moeller, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Obesity arises from a neurobehavioral disorder in which the brain’s regulation of hunger and food intake is impaired, leading to an imbalance between energy consumption and expenditure. One key phenotype associated with obesity is body mass index (BMI). BMI is influenced by multiple causal pathways driven by behavioral, metabolic, and genetic factors. Traditional obesity prediction studies often rely on magnetic resonance imaging (MRI) voxel-based morphometry to correlate BMI with obesity-related clinical measurements and brain structure, predominantly gray matter volume (GMV). However, the altered brain regions are variable and widespread between studies, with some literature presenting contradictory results between BMI and …

Adiposity Throughout Adulthood And Risk Of Young-Onset Breast Cancer Tumor Subtypes In The Young Women's Health History Study, Lydia Marcus Post, Dorothy R. Pathak, Ann S. Hamilton, Kelly A. Hirko, Richard T. Houang, Emily H. Guseman, Dan Sanfelippo, Nicole Bohme Carnegie, L. Karl Olson, Hallgeir Rui, Ann G. Schwartz, Ellen M. Velie

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: The role of adult adiposity in young-onset breast cancer (YOBC) subtype risk is not well understood.

METHODS: In this population-based case (n = 1812)-control (n = 1,381) study of invasive YOBC (ages <50 >years), cases were identified from the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results registries, 2010 to 2015. Area-based, frequency-matched controls were sampled from the 2010 Census. General adiposity [body mass index (BMI)] and central adiposity (waist circumference and waist-to-height ratio) across adulthood and covariates were collected from in-person interviews and measurements. ORs and 95% confidence intervals (CI) for adiposity and YOBC tumor subtypes …

Hunting For Heroes: Brain Neurons Mediating Glp-1r Agonists In Obesity Treatment, Yuhan Cao, Qingchun Tong

Faculty, Staff and Student Publications

Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) have proven to be highly effective in reducing obesity across species and ages, gaining unmet popularity in clinical treatments against obesity. Although extensive research efforts have been made to explore how the brain regulates body weight homeostasis including the effect brought up by GLP-1 and its synthetic analogs GLP-1RAs, the identity of neurons and neural pathways that are responsible for the observed anti-obesity effect of GLP-1RAs remain largely elusive. Excitingly, three recent high-profile studies presented compelling evidence that each argues for the importance of GLP-1Rs in the dorsomedial hypothalamus, hindbrain, or lateral septum, …