Endocrine System Diseases Commons^™

Association Of Type 2 Diabetes Subgroups With Cognitive Status Without Modification From Lifestyle Intervention, Michael P Bancks, James Lovato, Ashok Balasubramanyam, Mace Coday, Karen C Johnson, Medha Munshi, Candida Rebello, Lynne E Wagenknecht, Mark A Espeland

Faculty, Staff and Students Publications

CONTEXT: Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown.

OBJECTIVE: We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD.

METHODS: We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with …

Prevention Of Obesity-Related Morbidity & Mortality In Adults, Rachelle Virgin

Masters Theses/Capstone Projects

Poster presentation on the prevention of obesity related morbidity and mortality in adults.

The Effects Of Racism And Resilience On Black Stroke- Survivor Quality Of Life: Study Protocol And Rationale For A Mixed-Methods Approach, Xiude Fan, Junming Han, Enfa Zhao, Jiansong Fang, Dawei Wang, Yiping Cheng, Yingzhou Shi, Zhen Wang, Zhenyu Yao, Peng Lu, Tianbao Liu, Qihang Li, Kyle L Poulsen, Zhongshang Yuan, Yongfeng Song, Jiajun Zhao

Faculty, Staff and Student Publications

Breakthrough SARS-CoV-2 infections of vaccinated individuals are being reported globally, resulting in an increased risk of hospitalization and death among such patients. Therefore, it is crucial to identify the modifiable risk factors that may affect the protective efficacy of vaccine use against the development of severe COVID-19 and thus to initiate early medical interventions. Here, in population-based studies using the UK Biobank database and the 2021 National Health Interview Survey (NHIS), we analyzed 20,362 participants aged 50 years or older and 2,588 aged 18 years or older from both databases who tested positive for SARS-COV-2, of whom 33.1% and 67.7% …

Long-Term Maternal Metabolic And Cardiovascular Phenotypes After A Pregnancy Complicated By Mild Gestational Diabetes Mellitus Or Obesity, Ashley N Battarbee, Lisa Mele, Mark B Landon, Michael W Varner, Brian M Casey, Uma M Reddy, Ronald J Wapner, Dwight J Rouse, John M Thorp, Edward K Chien, George Saade, Beth A Plunkett, Sean C Blackwell

Faculty, Staff and Student Publications

Objective:

To evaluate the association of mild gestational diabetes (GDM) and obesity with metabolic and cardiovascular markers 5-10 years after pregnancy.

Study Design:

This was a secondary analysis of 5-10 year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/HOMA-IR, and cardiovascular markers VEGF, VCAM-1, CD40L, GDF-15, and ST-2. Multivariable linear regression estimated the association of GDM and obesity …

Non-Pharmaceutical Symptom Management In Patients With Pcos, Allison Stern

Capstone Showcase

Polycystic Ovarian Syndrome (PCOS) is a relatively common diagnosis among biological females. There are many variations of presentations among patients with PCOS that require an individualized and tailored treatment plan for symptom management. Although there are pharmaceutical medications that can be used for PCOS symptoms, some patients’ symptoms might not be fully managed, or they might prefer to focus on non-pharmaceutical options for their symptoms instead. Therefore, it is important for clinicians to be familiar with alternatives to the mainstay of pharmaceutical treatment.

The Short- And Long-Term Readmission Of Four Major Categories Of Digestive System Cancers: Does Obesity Or Metabolic Disorder Matter?, Yan Li, Xiaoqin Wu, Yongfeng Song, Peipei Wang, Bofei Zhang, Bingzhou Guo, Ziwei Liu, Yafei Wu, Shanshan Shao, Yiping Cheng, Honglin Guo, Xiude Fan, Jiajun Zhao

Faculty, Staff and Student Publications

Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC.

Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox …

Weight Strategy In Older Adults With Obesity: Calorie Restriction Or Not?, Georgia Colleluori, Dennis T Villareal

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Along with the marked increase in the population of older adults with obesity is the need for effective strategies to treat aging- and obesity-related complications. This review highlights recent progress in obesity management in older adults.

RECENT FINDINGS: Although calorie restriction is needed to significantly reduce fat mass, an exercise protocol is crucial to ameliorate functional outcomes. The addition of a resistance exercise protocol improves the response of muscle protein synthesis to anabolic stimuli, preventing the calorie restriction-induced reduction in muscle and bone mass. The addition of an aerobic exercise protocol improves cardiorespiratory fitness and cognitive function. …

Development Of A Clinical Prediction Model For Diabetes In Chronic Pancreatitis: The Predict3c Study, Christie Jeon, Phil A Hart, Liang Li, Yunlong Yang, Eleanor Chang, Melena D Bellin, William E Fisher, Evan L Fogel, Christopher E Forsmark, Walter G Park, Stephen K Van Den Eeden, Santhi Swaroop Vege, Jose Serrano, David C Whitcomb, Dana K Andersen, Darwin L Conwell, Dhiraj Yadav, Mark O Goodarzi

Faculty, Staff and Students Publications

OBJECTIVE: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.

RESEARCH DESIGN AND METHODS: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was …

Indices Of Sarcopenic Obesity Are Important Predictors Of Finite Element Analysis-Derived Bone Strength In Older Adults With Obesity, Giulia Gregori, Arjun Paudyal, Yoann Barnouin, Alessandra Celli, Martha Belen Segoviano-Escobar, Reina Armamento-Villareal, Nicola Napoli, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

BACKGROUND: The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT).

METHODS: One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m

RESULTS: Both ALM/W and HGS were positively correlated explaining 28% …

Weekly Telehealth Weigh-In For Bmi Reduction, Kelly Ahmad

Student Scholarly Projects

Practice Problem: The citizens of the United States are known for being overweight or obese. The Centers for Disease Control and Prevention (CDC, 2021) reported that approximately 74% of adults are either overweight or obese. PICOT: The PICOT question that guided this project was In overweight adults (P), does telemonitoring weekly for counseling and weigh-in (I) compared to current practice (C) decrease BMI over an 8-week period of time (T)? Evidence: The citizens of the United States are known for being overweight or obese. The Centers for Disease Control and Prevention (CDC, 2021) reported that approximately 74% of …

Dawn-To-Dusk Dry Fasting Induces Anti-Atherosclerotic, Anti-Inflammatory, And Anti-Tumorigenic Proteome In Peripheral Blood Mononuclear Cells In Subjects With Metabolic Syndrome, Ayse L Mindikoglu, Jihwan Park, Antone R Opekun, Mustafa M Abdulsada, Zoe R Wilhelm, Prasun K Jalal, Sridevi Devaraj, Sung Yun Jung

Faculty, Staff and Students Publications

BACKGROUND: Metabolic syndrome characterized by abdominal obesity, high blood pressure, elevated fasting glucose and triglyceride levels and low high-density lipoprotein cholesterol level is associated with pro-inflammatory state, increased risk for atherosclerosis, and multiple cancers. Our previous results on subjects with metabolic syndrome showed that 4-week dawn-to-dusk (sunset) dry fasting resulted in significant changes in the serum proteome and improvement in several metabolic risk factors. Peripheral blood mononuclear cells (PBMC) proteomics is a powerful tool that can provide mechanistic insights into how dawn-to-dusk dry fasting affects protein expression in metabolic pathways at cellular level. In this study, we determined whether dawn-to-dusk …

The Roles Of Sleep And Eating Patterns In Adiposity Gain Among Preschool-Aged Children, Amy R Goetz, Ishita Jindal, Jennette P Moreno, Maurice R Puyau, Anne L Adolph, Salma Musaad, Nancy F Butte, Fida Bacha

Faculty, Staff and Students Publications

BACKGROUND: Short sleep durations are related to risks for obesity in preschool children. However, the underlying mechanism or mechanisms are not clear.

OBJECTIVES: We evaluated the relationships between sleep characteristics and body composition, energetics, and weight-regulating behaviors in preschool-aged children, as well as the longitudinal associations between children's sleep and eating patterns and body composition at a 1-year follow-up.

METHODS: Data were drawn from a longitudinal study of 118 children aged 3-5 years. Sleep (duration, midpoint, regularity) and physical activity (PA) were measured by accelerometry over 6 consecutive days; total energy expenditure (TEE) was measured using the doubly labeled water …

Does Crime Trigger Genetic Risk For Type 2 Diabetes In Young Adults? A G X E Interaction Study Using National Data, Fangqi Guo, Kathleen Mullan Harris, Jason D. Boardman, Jennifer W. Robinette

Psychology Faculty Articles and Research

Background

Living in neighborhoods perceived as disordered exacerbates genetic risk for type 2 diabetes (T2D) among older adults. It is unknown whether this gene-neighborhood interaction extends to younger adults. The present study aims to investigate whether crime, an objectively measured indicator of neighborhood disorder, triggers genetic risk for T2D among younger adults, and whether this hypothesized triggering occurs through exposure to obesity.

Methods

Data were from the Wave I (2008) National Longitudinal Study of Adolescent to Adult Health. A standardized T2D polygenic score was created using 2014 GWAS meta-analysis results. Weighted mediation analyses using generalized structural equation models were conducted …

Investigating The Correlation Between Lpr & Obesity, Andrew S. Franklin Bs, Chad A. Nieri Bs, M. Boyd Gillespie Md

Longitudinal Scholar's Project

Objectives: To determine whether Drug-Induced Sleep Endoscopy (DISE) findings of Laryngopharyngeal Reflux (LPR) correlate with obesity, gender, Epworth Sleepiness scale, and OSA severity.

Study design: Single center retrospective cohort study.

Methods: Patients greater than 18 years of age who underwent DISE by one surgeon at a tertiary care center from July 2016 to July 2022 were included. DISE findings, patient characteristics, demographics, polysomnogram(s), and Epworth Sleepiness Scale(s) were extracted. Fisher’s exact test was used to compare categorical variables, and independent sample t-test was used to compare continuous variables. All statistical analyses were performed using IBM SPSS Statistics 28.

Results: …

Activating Connexin43 Gap Junctions Primes Adipose Tissue For Therapeutic Intervention, Yi Zhu, Na Li, Mingyang Huang, Xi Chen, Yu A An, Jianping Li, Shangang Zhao, Jan-Bernd Funcke, Jianhong Cao, Zhenyan He, Qingzhang Zhu, Zhuzhen Zhang, Zhao V Wang, Lin Xu, Kevin W Williams, Chien Li, Kevin Grove, Philipp E Scherer

Faculty, Staff and Students Publications

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic …

An Exercise-Inducible Metabolite That Suppresses Feeding And Obesity, Veronica L Li, Yang He, Kévin Contrepois, Hailan Liu, Joon T Kim, Amanda L Wiggenhorn, Julia T Tanzo, Alan Sheng-Hwa Tung, Xuchao Lyu, Peter-James H Zushin, Robert S Jansen, Basil Michael, Kang Yong Loh, Andrew C Yang, Christian S Carl, Christian T Voldstedlund, Wei Wei, Stephanie M Terrell, Benjamin C Moeller, Rick M Arthur, Gareth A Wallis, Koen Van De Wetering, Andreas Stahl, Bente Kiens, Erik A Richter, Steven M Banik, Michael P Snyder, Yong Xu, Jonathan Z Long

Children’s Nutrition Research Center Staff Publications

Exercise confers robust protection against obesity, type 2 diabetes, and other cardiometabolic diseases.1–5 However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear.6 Here we show that exercise stimulates production of Lac-Phe, a blood-borne signaling metabolite that suppresses feeding and obesity. Lac-Phe biosynthesis from lactate occurs in CNDP2+ cells including immune cells, epithelial cells, and mesenchymal stem cells localized to diverse organs. In diet-induced obese mice, pharmacological elevation of circulating Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and …

Constitutive Loss Of Dnmt3a Causes Morbid Obesity Through Misregulation Of Adipogenesis, Ayala Tovy, Jaime M Reyes, Linda Zhang, Yung-Hsin Huang, Carina Rosas, Alexes C Daquinag, Anna Guzman, Raghav Ramabadran, Chun-Wei Chen, Tianpeng Gu, Sinjini Gupta, Laura Ortinau, Dongsu Park, Aaron R Cox, Rachel E Rau, Sean M Hartig, Mikhail G Kolonin, Margaret A Goodell

Faculty, Staff and Students Publications

DNA Methyltransferase 3 A (DNMT3A) is an important facilitator of differentiation of both embryonic and hematopoietic stem cells. Heterozygous germline mutations in DNMT3A lead to Tatton-Brown-Rahman Syndrome (TBRS), characterized by obesity and excessive height. While DNMT3A is known to impact feeding behavior via the hypothalamus, here we investigated a role in adipocyte progenitors utilizing heterozygous knockout mice that recapitulate cardinal TBRS phenotypes. These mice become morbidly obese due to adipocyte enlargement and tissue expansion. Adipose tissue in these mice exhibited defects in preadipocyte maturation and precocious activation of inflammatory gene networks, including interleukin-6 signaling. Adipocyte progenitor cell lines lacking DNMT3A …

Berberine Remodels Adipose Tissue To Attenuate Metabolic Disorders By Activating Sirtuin 3, Dan Li, Chao Yang, Jian-Zhong Zhu, Eduardo Lopez, Tian Zhang, Qiang Tong, Cheng Peng, Li-Gen Lin

Faculty, Staff and Students Publications

Adipose tissue remodelling is considered a critical pathophysiological hallmark of obesity and related metabolic diseases. Berberine (BBR), a natural isoquinoline alkaloid, has potent anti-hyperlipidaemic and anti-hyperglycaemic effects. This study aimed to explore the role of BBR in modulating adipose tissue remodelling and the underlying mechanisms. BBR protected high fat diet (HFD)-fed mice against adiposity, insulin resistance and hyperlipidemia. BBR alleviated adipose tissue inflammation and fibrosis by inhibiting macrophage infiltration, pro-inflammatory macrophage polarization and the abnormal deposition of extracellular matrix, and the effect was mediated by BBR directly binding and activating the deacetylase Sirtuin 3 (SIRT3) and suppressing the activation of …

Type 2 Diabetes Partitioned Polygenic Scores Associate With Disease Outcomes In 454,193 Individuals Across 13 Cohorts, Daniel Dicorpo, Jessica Leclair, Joanne B Cole, Chloé Sarnowski, Fariba Ahmadizar, Lawrence F Bielak, Anneke Blokstra, Erwin P Bottinger, Layal Chaker, Yii-Der I Chen, Ye Chen, Paul S De Vries, Tariq Faquih, Mohsen Ghanbari, Valborg Gudmundsdottir, Xiuqing Guo, Natalie R Hasbani, Dorina Ibi, M Arfan Ikram, Maryam Kavousi, Hampton L Leonard, Aaron Leong, Josep M Mercader, Alanna C Morrison, Girish N Nadkarni, Mike A Nalls, Raymond Noordam, Michael Preuss, Jennifer A Smith, Stella Trompet, Petra Vissink, Jie Yao, Wei Zhao, Eric Boerwinkle, Mark O Goodarzi, Vilmundur Gudnason, J Wouter Jukema, Sharon L R Kardia, Ruth J F Loos, Ching-Ti Liu, Alisa K Manning, Dennis Mook-Kanamori, James S Pankow, H Susan J Picavet, Naveed Sattar, Eleanor M Simonsick, W M Monique Verschuren, Ko Willems Van Dijk, Jose C Florez, Jerome I Rotter, James B Meigs, Josée Dupuis, Miriam S Udler

Faculty, Staff and Student Publications

OBJECTIVE: Type 2 diabetes (T2D) has heterogeneous patient clinical characteristics and outcomes. In previous work, we investigated the genetic basis of this heterogeneity by clustering 94 T2D genetic loci using their associations with 47 diabetes-related traits and identified five clusters, termed β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. The relationship between these clusters and individual-level metabolic disease outcomes has not been assessed.

RESEARCH DESIGN AND METHODS: Here we constructed individual-level partitioned polygenic scores (pPS) for these five clusters in 12 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (n = 454,193) …

Paraventricular Vitamin D Receptors Are Required For Glucose Tolerance In Males But Not Females, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Gabrielle Phillips, Yanlin He, Stephanie Sisley

Faculty, Staff and Students Publications

When delivered directly into the brain, vitamin D, can improve glucose levels in male mice. Additionally, the loss of the vitamin D receptor (VDR) in male mice's paraventricular hypothalamus (PVH) results in impaired glucose tolerance. Data in humans shows that low vitamin D levels are detrimental to glucose homeostasis, an effect that may be more prominent in men. However, it is unknown if vitamin D action in the brain is required for normal glucose regulation in female mice. This study shows that in both viral and genetic models, male mice with obesity and PVH VDR loss have impaired glucose tolerance …

De Novo Glycine Synthesis Is Reduced In Adults With Morbid Obesity And Increases Following Bariatric Surgery, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Chun Fan Lee, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance.

OBJECTIVE: Using multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI ≥ 32.5 kg/m

METHODS: [1,2-

RESULTS: Compared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced

CONCLUSION: Hypoglycinemia …

Hypothalamic Steroid Receptor Coactivator-2 Regulates Adaptations To Fasting And Overnutrition, Yongjie Yang, Yanlin He, Hailan Liu, Wenjun Zhou, Chunmei Wang, Pingwen Xu, Xing Cai, Hesong Liu, Kaifan Yu, Zhou Pei, Ilirjana Hyseni, Makoto Fukuda, Qingchun Tong, Jianming Xu, Zheng Sun, Bert W O'Malley, Yong Xu

Faculty, Staff and Students Publications

The neuroendocrine system coordinates metabolic and behavioral adaptations to fasting, including reducing energy expenditure, promoting counterregulation, and suppressing satiation and anxiety to engage refeeding. Here, we show that steroid receptor coactivator-2 (SRC-2) in pro-opiomelanocortin (POMC) neurons is a key regulator of all these responses to fasting. POMC-specific deletion of SRC-2 enhances the basal excitability of POMC neurons; mutant mice fail to efficiently suppress energy expenditure during food deprivation. SRC-2 deficiency blunts electric responses of POMC neurons to glucose fluctuations, causing impaired counterregulation. When food becomes available, these mutant mice show insufficient refeeding associated with enhanced satiation and discoordination of anxiety …

The Physiological Benefits Of A Plant-Based Diet On Cardiovascular Health, Jenevieve Petray

Nursing | Senior Theses

Cardiovascular disease (CVD) is increasingly more prevalent in today’s society and is attributed to an alarming percentage of American hospitalizations and deaths. Americans are unhealthier than ever before, and the main contributor is the Western diet. Diet is a double-edged sword that can offer benefits or detriments to one’s health. CVD encompasses numerous diagnoses originating from various underlying physiological alterations. These alterations are downstream effects of increased body weight and BMI, increased cholesterol levels, decreased insulin sensitivity and increased arterial plaque buildup. Research shows that a plant-based diet has the potential to manage and reverse all fundamental physiological alterations that …

Hiv-1 Viral Protein R Couples Metabolic Inflexibility With White Adipose Tissue Thermogenesis, Neeti Agarwal, Dinakar Iyer, Pradip Saha, Aaron R Cox, Yan Xia, Netanya S Utay, Anoma Somasundaram, Ulrich Schubert, Jordan E Lake, Sean M Hartig, Ashok Balasubramanyam

Faculty, Staff and Students Publications

Persons living with HIV (PLWH) manifest chronic disorders of brown and white adipose tissues that lead to diabetes and metabolic syndrome. The mechanisms that link viral factors to defective adipose tissue function and abnormal energy balance in PLWH remain incompletely understood. Here, we explored how the HIV accessory protein viral protein R (Vpr) contributes to adaptive thermogenesis in two mouse models and human adipose tissues. Uncoupling protein 1 (UCP1) gene expression was strongly increased in subcutaneous white adipose tissue (WAT) biopsy specimens from PLWH and in subcutaneous WAT of the Vpr mice, with nearly equivalent mRNA copy number. Histology and …

Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Na Li, Mingyang Huang, Mason Bartels, Sophie Dogné, Shangang Zhao, Xi Chen, Clair Crewe, Leon Straub, Lavanya Vishvanath, Zhuzhen Zhang, Mengle Shao, Yongjie Yang, Christy M Gliniak, Ruth Gordillo, Gordon I Smith, William L Holland, Rana K Gupta, Bingning Dong, Nathalie Caron, Yong Xu, Yucel Akgul, Samuel Klein, Philipp E Scherer

Faculty, Staff and Students Publications

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma …

High Burden Of Subclinical And Cardiovascular Disease Risk In Adults With Metabolically Healthy Obesity: The Atherosclerosis Risk In Communities (Aric) Study, Yvonne Commodore-Mensah, Mariana Lazo, Olive Tang, Justin B Echouffo-Tcheugui, Chiadi E Ndumele, Vijay Nambi, Dan Wang, Christie Ballantyne, Elizabeth Selvin

Faculty, Staff and Students Publications

OBJECTIVE: It is controversial whether adults who are obese but "metabolically healthy" have cardiovascular disease (CVD) risk comparable with that of normal-weight adults. High-sensitivity cardiac troponin T (hs-cTnT), a biomarker of myocardial damage, is useful in characterizing subclinical CVD. We categorized obesity phenotypes and studied their associations with subclinical and clinical CVD and CVD subtypes, including heart failure (HF).

RESEARCH DESIGN AND METHODS: We conducted cross-sectional and prospective analyses of 9,477 adults in the Atherosclerosis Risk in Communities (ARIC) study. We used the Adult Treatment Panel III criteria and BMI to define obesity phenotypes as follows: metabolically healthy normal weight, …

Rap1 In The Vmh Regulates Glucose Homeostasis, Kentaro Kaneko, Hsiao-Yun Lin, Yukiko Fu, Pradip K Saha, Ana B De La Puente-Gomez, Yong Xu, Kousaku Ohinata, Peter Chen, Alexei Morozov, Makoto Fukuda

Faculty, Staff and Students Publications

The hypothalamus is a critical regulator of glucose metabolism and is capable of correcting diabetes conditions independently of an effect on energy balance. The small GTPase Rap1 in the forebrain is implicated in high-fat diet-induced (HFD-induced) obesity and glucose imbalance. Here, we report that increasing Rap1 activity selectively in the medial hypothalamus elevated blood glucose without increasing the body weight of HFD-fed mice. In contrast, decreasing hypothalamic Rap1 activity protected mice from diet-induced hyperglycemia but did not prevent weight gain. The remarkable glycemic effect of Rap1 was reproduced when Rap1 was specifically deleted in steroidogenic factor-1-positive (SF-1-positive) neurons in the …

Type 2 Diabetes Subgroups, Risk For Complications, And Differential Effects Due To An Intensive Lifestyle Intervention, Michael P Bancks, Haiying Chen, Ashok Balasubramanyam, Alain G Bertoni, Mark A Espeland, Steven E Kahn, Scott Pilla, Elizabeth Vaughan, Lynne E Wagenknecht

Faculty, Staff and Students Publications

OBJECTIVE: We reevaluated the Action for Health in Diabetes (Look AHEAD) intervention, incorporating diabetes subgroups, to identify whether intensive lifestyle intervention (ILI) is associated with differential risk for cardiovascular disease (CVD) by diabetes subgroup.

RESEARCH DESIGN AND METHODS: In the Look AHEAD trial, 5,145 participants, aged 45-76 years, with type 2 diabetes (T2D) and overweight or obesity were randomly assigned to 10 years of ILI or a control condition of diabetes support and education. The ILI focused on weight loss through decreased caloric intake and increased physical activity. To characterize diabetes subgroups, we applied k-means clustering to data on age …

In Men With Obesity, T2dm Is Associated With Poor Trabecular Microarchitecture And Bone Strength And Low Bone Turnover, Francesca Vigevano, Giulia Gregori, Georgia Colleluori, Rui Chen, Vimlin Autemrongsawat, Nicola Napoli, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

INTRODUCTION: Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture, and strength in the obese population remains unknown.

METHODS: Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay, body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry, whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography. Data were compared among metabolically healthy obese (MHO) and metabolically …

The Bile Acid Induced Hepatokine Orosomucoid Suppresses Adipocyte Differentiation, Sung Ho Lee, Jong Min Choi, Sung Yun Jung, Aaron R Cox, Sean M Hartig, David D Moore, Kang Ho Kim

Faculty, Staff and Students Publications

Bile acids have recently emerged as key metabolic hormones with beneficial impacts in multiple metabolic diseases. We previously discovered that hepatic bile acid overload distally modulates glucose and fatty acid metabolism in adipose tissues to exert anti-obesity effects. However, the detailed mechanisms that explain the salutary effects of serum bile acid elevation remain unclear. Here, proteomic profiling identified a new hepatokine, Orosomucoid (ORM) that governs liver-adipose tissue crosstalk. Hepatic ORMs were highly induced by both genetic and dietary bile acid overload. To address the direct metabolic effects of ORM, purified ORM proteins were administered during adipogenic differentiation of 3T3-L1 cells …