Medical Pharmacology Commons^™

Kinase Signaling In Liver Disease Via Clinical-Trial-On-A-Pamchip: A Distinctive Methodology For Drug Mechanisms And Personalized Medicine, Zachary A. Kipp, Evelyn A. Bates, Genesee J. Martinez, Wang-Hsin Lee, Sally N. Pauss, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

The utilization of extensive datasets, such as those generated by DNA or RNA sequencing, has become a central focus in drug discovery and personalized medicine (PerMed). Nonetheless, these datasets are constrained by the absence of protein-functionality testing, which affects physiological responses. In this study, we employed PamGene PamStation technology to quantify protein function by kinase activity across more than 500 signaling pathways from patients with hepatocellular carcinoma (HCC). Using proteins derived from nine patients and five human HCC cell lines for drug discovery and the clinical trial-on-a-chip approach, we developed comprehensive PerMed scores from the PamStation data to differentiate individual …

A Ubiquitous Organophosphate Flame Retardant Disrupts Energy And Glucose Homeostasis In Mice, Krystal M. Sewell, Kelly Oriakhi, Sara Y. Ngo Tenlep, Megan L. Weaver, Mansura Shahad Bawa, Se-Hyung Park, Shubh Saraswat, Xiaohua D. Zhang, Robert N. Helsley, Samir Softic, Cetewayo S. Rashid

Pharmacology and Nutritional Sciences Faculty Publications

Organophosphate flame retardants (OPFRs) are used in many consumer products, and their presence in our environment raises concerns about potential health dangers. In humans, exposure to OPFRs, such as tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is associated with metabolic disorders such as obesity, hyperglycemia, and insulin resistance. Our current study seeks to determine how TDCPP exposure affects body composition, glucose homeostasis, and energy balance in a rodent model. C57Bl/6 J mice were divided into two weight-matched groups and fed purified low phytoestrogen diets containing either 0.1 % DMSO (control) or TDCPP 415 mg/kg resulting in an approximate exposure of 50 mg/kg/day. Both male …

Contribution Of Metabolism-Independent Glucose Sensing To Metabolic Homeostasis, Nadia Rashid, Kavaljit H. Chhabra

Pharmacology and Nutritional Sciences Faculty Publications

Glucose sensing and signaling are central to cellular metabolic machinery for the regulation of metabolic homeostasis. Glucose sensing has been almost always assumed to be coupled with glucose metabolism; however, recent findings have unraveled metabolism-independent sensing mechanisms. Here, we discuss whether glucose transporters (GLUTs) and sodium-glucose co-transporters (SGLTs) may also function as glucose sensors independent of their roles in transporting glucose. Moreover, we review the emerging roles of G protein-coupled receptors (GPCRs) in sensing glucose and, consequently, initiating its signaling pathways in a cell-specific manner. Altogether, this review offers insights into the newly identified glucose sensing mechanisms and highlights the …

Anatomical Atlas Of Kinase Responsiveness To Weight Gain: Adipose Depot Reprogramming In Diet-Induced Adiposity, Wang-Hsin Lee, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Mei Xu, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

Background/Objectives: Adipose tissue depots located at different anatomical sites exert differential functions in response to adiposity and glucose intolerance. These fat depots exhibit distinct metabolic signaling patterns that may influence pathological fat accumulation, thereby affecting the efficacy of anti-obesity interventions. Nonetheless, the mechanisms underpinning depot-specific signaling and pathway responsiveness remain insufficiently understood.

Methods: Kinase activity was characterized during the progression of adiposity across five adipose tissue depots in obese versus lean mice using the advanced PamGene kinome technology. Furthermore, kinase pathways in human preadipocytes and mouse 3T3-L1 preadipocytes were analyzed and compared with those in their differentiated, mature adipocytes. The …

The Mitochondria As An Emerging Target Of Self- Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly, Evelyn Winter, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

Acute lymphocytic leukemia (ALL) is the most common leukemia in children, with the T-cell subtype (T- ALL) accounting for 15% of those cases. Despite advancements in the treatment of T-ALL, patients still face a dismal prognosis following their first relapse. Relapse can be attributed to the inability of chemotherapy agents to eradicate leukemia stem cells (LSC), which possess self-renewal capabilities and are responsible for the long-term maintenance of the disease. Mitochondria have been recognized as a therapeutic vulnerability for cancer stem cells, including LSCs. Mitocans have shown promise in T-ALL both in vitro and in vivo, with some currently in …

Astrovascular Decoupling In Awake 5×Fad Mice Is Associated With Reduced Astrocytic Calcium, Ruei-Lung Lin, Sophiya L. Sims, Nicholas A. Wright, Léopoldine B. Galopin, Blaine Weiss, Susan D. Kraner, Jacquelyn E. Rhinehart, Ting-Hsuan Lu, Pradoldej Sompol, Christopher M. Norris, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

INTRODUCTION

Evidence points to dysregulated Ca²⁺ in neurons and astrocytes in models of amyloidosis. While most of these data were obtained in vitro or in vivo under anesthesia, less work has investigated these variables in awake ambulating mice.

METHODS

Astrocytic Ca²⁺ fluctuations (GCaMP8f) were imaged concomitantly with vasoreactivity in S1 on a two-photon microscope during rest and ambulation. Single-cell resolution variables were extracted using continuous wavelet transform and traditional ΔF/F measures.

RESULTS

Along with increases in amyloid beta (Aβ) accumulation, we found significant reductions in measures of astrocyte functional connectivity, pairwise correlations, and network synchronicity in older 5×FAD …

Advancing Clinical Trial Readiness In White Matter Disease And Related Dementias: Key Steps For Future Research Progress, Pradoldej Sompol, Gregory A. Jicha, Jason D. Hinman, Adam M. Brickman, Steven M. Greenberg, Konstantinos Arfanakis, Marion S. Buckwalter, Irene Lorenzo Llorente, Jeff D. Williamson, Michael S. Wolf, Eric E. Smith, Aditi Gupta, Margaret E. Flanagan, Miguel A. Vazquez, Jeffrey M. Burns, S. Thomas Carmichael, Frank C. Barone

Pharmacology and Nutritional Sciences Faculty Publications

White matter disease, a broad-spectrum term that covers various types of white matter lesions and degeneration, is strongly related to age-related neurodegenerative disorders including Alzheimer’s disease (AD), and vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer’s related dementias (ADRD). There is no specific treatment for white matter disease. Therefore, basic research and clinical studies are essential for future outcomes. Since its formation in 2020, the Albert Research Institute for White Matter and Cognition (ARIWMC) mission has been to support white matter research by providing a forum for communication where basic and clinical scientists meet to discuss and debate …

Targeting Prmt5 In Inflammation And Cancer: A Nexus Of Endotoxin Signaling, Antigen Presentation And Immune Evasion., Jimmy James Msemo

Theses and Dissertations--Medical Sciences

Protein Arginine Methyltransferase 5 (PRMT5) is a member of PRMT family that controls both intrinsic and extrinsic oncogenic processes [1]. Protein arginine methyltransferase 5 (PRMT5) is a type II methyltransferase that exerts widespread influence over gene expression, splicing, DNA repair, and immune regulation through symmetric dimethylation of arginine residues on histone and non-histone proteins [2]. The addition of methyl groups induces gene silencing through producing dictatorial histone marks like H2AR3ne2s, H3R8me2s and H4R3mes [3], which act as epigenetic repressive marks on gene promoters. In non-histone proteins, PRMT5 can methylate and regulate transcription factor proteins such as p53, E2F1, and p65, …

A Unique Inflammaging Profile Generated By T Cells From People With Obesity Is Metformin Resistant, S. Santacruz‑Calvo, S. Saraswat, Gabriella Kalantar, E. Zukowski, H. Marszalkowski, Aida Javidan, F. Gholamrezaeinejad, L. P. Bharath, P. A. Kern, X. D. Zhang, Barbara S. Nikolajczyk

Pharmacology and Nutritional Sciences Faculty Publications

The alarmingly high prevalence of obesity in older adults coupled with the negative health effects of chronic inflammation in both obesity and aging highlight the importance of studies investigating the impacts of obesity on age-related inflammation. Since shifts in peripheral T-cell metabolism and function drive systemic inflammation in both obesity and aging, we hypothesize that obesity impacts the Th17-dominated inflammaging profile we identified in lean subjects and thus modifies the anti-inflammatory effects of geroprotective drugs like metformin. New cytokine profiling data showed that CD4+ T cells from older people with obesity generate a profile that specifically excludes Th17 cytokines. Metformin …

Bilirubin Hepatic And Intestinal Transport And Catabolism: Physiology, Pathophysiology, And Benefits, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Terry D. Hinds, Jr., Wang-Hsin Lee

Pharmacology and Nutritional Sciences Faculty Publications

Bilirubin, a metabolite derived from heme degradation, has traditionally been regarded as a waste product and a marker of liver injury. However, increasing evidence suggests that bilirubin also functions as a hormone, and reduced levels are associated with metabolic dysfunction. Studies have shown a strong association between low circulating bilirubin levels and an increased risk of metabolic disorders and cardiovascular disease. To advance bilirubin-based treatment strategies, it is essential to elucidate the mechanisms underlying bilirubin transport and metabolism. Therefore, we provide an in-depth discussion of bilirubin production and its subsequent fates, with a particular focus on the transport between the …

Cd47: An Immunoregulatory Nexus In Liver And Gastrointestinal Disorders, Josephine Otuagomah, Alana Newcomb, Taesik Gwag, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Cluster of differentiation 47 (CD47) is a widely expressed transmembrane protein that serves as a critical immunoregulatory checkpoint in both homeostatic and pathological conditions of the digestive system. It interacts with signal regulatory protein alpha to send a ‘do not eat me’ signal, thereby preventing phagocytosis and shaping immune responses. Beyond immunity, CD47 also influences cell death, growth and metabolism through interactions with integrins and thrombospondin-1. Recent studies implicate CD47 as a central nexus in the pathogenesis of diverse liver and gastrointestinal disorders, including metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis, inflammatory bowel disease, liver ischaemia-reperfusion injury, drug-induced liver …

Gut Microbiome, Neuroinflammation, And Fetal Alcohol Spectrum Disorders: Insights From Rodent Models, Abdulrahman M. Busayli, Wenhua Xu, Ghaidaa A. Raffah, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorder (FASD) is a significant public health issue that affects children. It results from ethanol exposure during pregnancy, leading to considerable physical, neurodevelopmental, behavioral, and cognitive deficits. The exact mechanism is not well understood. Recently, considerable attention has been focused on the influence of gut microbiome on brain development through the gut–brain axis. Changes in the gut microbiome resulting from ethanol exposure may contribute to the pathology of FASD, potentially involving neuroinflammation. This literature review summarizes the existing research and primary animal studies on the impact of early ethanol exposure on the gut microbiome, neuroinflammation, brain development, …

Calcineurin/Nfat Inhibitors Maintain Cognition In A Preclinical Prevention Study In An Aging Canine Model Of Alzheimer Disease, Lorena Sordo, Margo F. Ubele, Kathy Boaz, Jennifer L. Mefford, Erin Dehnart Jones, Katie L. Mccarty, Hollie Y. Van Rooyen, Jeffrey R. Smiley, Stasia A. Bembenek Bailey, Jessica A. Perpich, Beverly Meacham, David K. Powell, Frederick Bresch, Jacob W. Crump, Michael J. Phelan, Jessica A. Noche, Craig E. Stark, László G. Puskás, Christopher M. Norris, Elizabeth Head

Pharmacology and Nutritional Sciences Faculty Publications

Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT) transcription factor increases in Alzheimer disease (AD) and is associated with synaptic loss, neurodegeneration, neuroinflammation, amyloid-β (Aβ) production, and cognitive decline. CN/NFAT inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic use of tacrolimus in transplant patients reduces risk of AD. Beagles naturally develop Aβ plaques and cognitive dysfunction. We evaluated the impact of FDA-approved CN inhibitor, tacrolimus, and experimental NFAT inhibitor, Q134R, on cognitive outcomes during a three-year prevention study in 37 middle-aged beagles. While beagles treated with CN/NFAT inhibitors showed differences in the pattern …

Adhesion G Protein-Coupled Receptor Latrophilin 1 (Adgrl1): A Novel Regulator Of Glucose And Energy Homeostasis., Kavaljit H Chhabra

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Protocol For A Feasibility Randomized Controlled Trial Of Gentle Yoga In Older Patients Discharged From Phase Ii Cardiac Rehabilitation, Geunyeong Cha, Misook L. Chung, Nicholas R. Heebner, Ulf G. Bronas, Martha J. Biddle, Chin-Yen Lin, Junghee Kang, Jia-Rong Wu, Jessica H. Thompson, Ashmita Thapa, Debra K. Moser

UK CARES Faculty Publications

Background: Physical activity (PA) is essential following an acute cardiac event. Cardiac rehabilitation (CR) is commonly prescribed, and PA after CR is recommended. Because of age-related changes in functional ability and multi-comorbidity, many older cardiac patients struggle to continue performing PA at home after CR. Depressive symptoms and anxiety are prevalent in cardiac patients and associated with poor self-care, including lack of daily PA. Yoga has been demonstrated to improve psychological and physical health outcomes in cardiac patients, but it is unknown whether yoga, modified for older CR patients – Gentle Yoga – is beneficial in managing psycho- logical distress …

Aggravated Ulcerative Colitis Via Circnlgn-Mediated Suppression Of Nuclear Actin Polymerization., William W Du, Chi Zhou, Hui Yang, Shuoyang Wen, Yu Chen, Eric X Chen, Xiuwei H. Yang, Feiya Li, Kevin Y Du, Hui Yuan, Ting Ye, Javeria Qadir, Burton B Yang

Pharmacology and Nutritional Sciences Faculty Publications

Colitis is a chronic bowel disease characterized by damage to the lining of the large intestine, with its precise underlying causes remaining incompletely understood. In this study, we provide evidence that circular RNA circNlgn plays a pivotal role in promoting the development of colitis. Colitis patients produce significant higher levels of circNlgn. Transgenic mice expressing circNlgn exhibit heightened susceptibility to colitis development and progression, primarily attributed to the presence of the protein isoform Nlgn173 encoded by circNlgn. Nlgn173 undergoes translocation into cell nuclei, where it interacts with actin, impeding the binding of actin-related protein 2 and 3 (Arp2/3) complex to …

Evaluation Of The Cellular And Physiologic Impact Of Mitomycin C On Colon Cancer, Hannah Mcdonald

Theses and Dissertations--Clinical and Translational Science

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) with Mitomycin C (MMC) has more than doubled the overall and disease-free survival in patients with peritoneal metastases (PM) due to colorectal cancer (CRC) over the past two decades. Although MMC is the most used HIPEC drug for PM due to CRC, dosing protocols vary dramatically between and within institutions across the world. Additionally, little is known about the impact of hyperthermia and MMC on intracellular pathways for CRC. The aim of this work is to determine the optimal dosing strategy in the clinical application of MMC and hyperthermia for treatment of …

Exenatide As Chronopharmacotherapy For T2dm Associated Complications: Targeting Nondipping Blood Pressure And Sleep Insufficiency, Aaron Chacon

Theses and Dissertations--Pharmacology and Nutritional Sciences

Although largely impacted by age, race and ethnicity, and socioeconomic factors, Type 2 Diabetes Mellitus (T2DM) is primarily driven by obesity, currently affecting ~30 million in the U.S and ~463 million globally. T2DM carries numerous complications, including high prevalence of hypertension and nondipping blood pressure (BP), sleep insufficiency and fragmentation. Nondipping BP is an inadequate drop in BP (≤ 10%) during sleeping hours compared with waking hours. Lending to this, sleep disturbance acts as both precursor and consequence of metabolic dysregulation, greatly impacting circadian rhythmicity. To model these conditions, we utilized diabetic (db/db) mice. These mice carry a point mutation …

Adgrl1 Is A Glucose Receptor Involved In Mediating Energy And Glucose Homeostasis, Kavaljit H Chhabra, Siresha Bathina, Tumininu S Faniyan, Dennis J Samuel, Muhammad Ummear Raza, Leticia Maria De Souza Cordeiro, Gonzalo Viana Di Prisco, Brady K Atwood, Jorge Robles, Lauren Bainbridge, Autumn Davis

Pharmacology and Nutritional Sciences Faculty Publications

AIMS/HYPOTHESIS: The brain is a major consumer of glucose as an energy source and regulates systemic glucose as well as energy balance. Although glucose transporters such as GLUT2 and sodium-glucose cotransporter 2 (SGLT2) are known to regulate glucose homeostasis and metabolism, the identity of a receptor that binds glucose to activate glucose signalling pathways in the brain is unknown. In this study, we aimed to discover a glucose receptor in the mouse hypothalamus.

METHODS: Here we used a high molecular mass glucose-biotin polymer to enrich glucose-bound mouse hypothalamic neurons through cell-based affinity chromatography. We then subjected the enriched neurons to …

Effect Of Mitochondrial Oxidative Stress On Regulatory T Cell Manufacturing For Clinical Application In Transplantation: Results From A Pilot Study, Roberto Gedaly, Gabriel Orozco, Lillie J. Lewis, Deepa Valvi, Fanny Chapelin, Aman Khurana, Giovanna E. Hidalgo, Aaron Shmookler, Aashutosh Tripathi, Cuiping Zhang, Joseph B. Zwischenberger, Francesc Marti

Markey Cancer Center Faculty Publications

The manufacturing process of regulatory T (Treg) cells for clinical application begins with the positive selection of CD25⁺ cells using superparamagnetic iron oxide nanoparticle (SPION)-conjugated anti-CD25 antibodies (spCD25) and immunomagnetic cell separation technology. Our findings revealed that the interaction of spCD25 with its cell target induced the internalization of the complex spCD25–interleukin-2 receptor. Accumulation of intracellular spCD25 triggered oxidative stress, causing delayed Treg expansion and temporary reduction in suppressor activity. This activation delay hindered the efficient generation of clinically competent cells. During this early phase, Treg cells exhibited elevated mitochondrial superoxide and lipid peroxidation levels, with a concomitant decrease …

Effectiveness And Implementation Of Mpath™-Crc: A Mobile Health System For Colorectal Cancer Screening, Anna C. Snavely, Kristie Foley, Ajay Dharod, Mark Dignan, Holly Brower, Elena Wright, David P. Miller Jr.

UK CARES Faculty Publications

Background Screening for colorectal cancer (CRC) is widely recommended but underused, even though CRC is the third most diagnosed cancer and the second leading cause of cancer death in the USA. The mPATH™ program is an iPad-based application designed to identify patients due for CRC screening, educate them on the commonly used screening tests, and help them select their best option, with the goal of increasing CRC screening rates.

Methods The mPATH™ program consists of questions asked of all adult patients at check-in (mPATH™-CheckIn), as well as a module specific for patients due for CRC screening (mPATH™-CRC). In this study, …

Tris(1,3-Dichloro-2-Propyl) Phosphate Is A Metabolism-Disrupting Chemical In Male Mice, Sara Y. Ngo Tenlep, Megan L. Weaver, Jianzhong Chen, Olga A. Vsevolozhskaya, Andrew J. Morris, Cetewayo S. Rashid

Pharmacology and Nutritional Sciences Faculty Publications

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an organophosphate flame retardant. The primary TDCPP metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), is detectable in the urine of over 90 % of Americans. Epidemiological studies show sex-specific associations between urinary BDCPP levels and metabolic syndrome, which is an established risk factor for type 2 diabetes, heart disease, and stroke. We used a mouse model to determine whether TDCPP exposure disrupts glucose homeostasis. Six-week old male and female C57BL/6J mice were given ad libitum access to diets containing vehicle (0.1 % DMSO) and TDCPP resulting in the following treatment groups: 0 mg/kg/day, 0.02 mg/kg/day, 1 mg/kg/day, or 100 …

The Effect Of An Educational Handout On Knowledge, Awareness And Attitudes Of Pre-Exposure Prophylaxis (Prep) Among Participants At A Needle And Syringe Exchange Site, Mckenzie Buckel

DNP Projects

Background: In 2018, the total number of HIV cases in the United States was 1.2 million. Almost 186,500 of these cases were attributed to intravenous drug use. With the adherence to pre-exposure prophylaxis (PrEP) there is approximately a 49% decrease in the rates of HIV among people who inject drugs and the most significant barrier to PrEP among this population is a lack of awareness and knowledge.

Objective: The purpose of this study was to determine participants’ of a needle and syringe exchange site knowledge, awareness and attitudes of PrEP after reviewing an educational handout about PrEP.

Methods: A quasi …

Ethanol Exposure Up-Regulates Pd-L1/Pd-1 Immune Checkpoint Pathway And Promotes Mammary Tumor Development, Wenhua Xu, Linqing Wu, Mei Xu, Jia Luo, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

Alcohol consumption in women enhances breast cancer incidence and ethanol is the main causal factor. Compromised host immunity through immunosuppression facilitates the development of many types of cancer, including breast cancer. Immune cells in breast tissues, particularly tumor-infiltrating CD8 cytotoxic T cells, play a critical role in the host anti-tumor immunity against breast tumorigenesis. These cytotoxic T cells are the major immune cells to carry out anti-tumor immunity through their cytotoxic effector function, which can be regulated by immune checkpoint pathways. The PD-1/PD-L1 pathway (the interaction between programmed death-1, PD-1, and its ligand, programmed deathligand 1, PD-L1) is the best …

Targeting Squalene Epoxidase Interrupts Homologous Recombination Via The Er Stress Response And Promotes Radiotherapy Efficacy, Zhipeng Hong, Tao Liu, Lingfeng Wan, Pengyan Fa, Pankaj Kumar, Yanan Cao, Chandra Bhushan Prasad, Zhaojun Qiu, Joseph Liu, Hongbing Wang, Zaibo Li, Qi-En Wang, Peixuan Guo, Deliang Guo, Ayse S. Yilmaz, Lanchun Lu, Ioanna Papandreou, Naduparambil K. Jacob, Chunhong Yan, Qing-Bai She

Pharmacology and Nutritional Sciences Faculty Publications

Over 50% of all patients with cancer are treated with radiotherapy. However, radiotherapy is often insufficient as a monotherapy and requires a nontoxic radiosensitizer. Squalene epoxidase (SQLE) controls cholesterol biosynthesis by converting squalene to 2,3-oxidosqualene. Given that SQLE is frequently overexpressed in human cancer, this study investigated the importance of SQLE in breast cancer and non–small cell lung cancer (NSCLC), two cancers often treated with radiotherapy. SQLE-positive IHC staining was observed in 68% of breast cancer and 56% of NSCLC specimens versus 15% and 25% in normal breast and lung tissue, respectively. Importantly, SQLE expression was an independent predictor of …

A Study Of The Analysis Of Hemp-Derived Oil Products: Development Of A Method For The Analysis Of Phytocannabinoids In Medicinal Products, Erin Johnson

Theses and Dissertations--Pharmacology and Nutritional Sciences

Human interactions with cannabis have a history spanning millennia as a source of fiber, food, and medicine. The plant came across Asia, Europe, and Africa with the movements of people and travelers eventually coming to the Americas with European explorers. In colonizing North America, cannabis fiber was key to the production of canvas and ropes for ships. Although fiber was the driver for cannabis production in the United States, medicinal uses were prevalent and propelled the eventual regulations. The Pure Food and Drug Act of 1906 mandated accurate labeling on drugs such as cannabis followed by the Marihuana Tax Act …

Adipose-Specific Pparα Knockout Mice Have Increased Lipogenesis By Pask–Srebp1 Signaling And A Polarity Shift To Inflammatory Macrophages In White Adipose Tissue, Terry D. Hinds, Jr., Zachary A. Kipp, Mei Xu, Frederique B. Yiannikouris, Andrew J. Morris, Donald F. Stec, Walter Wahli, David E. Stec

Pharmacology and Nutritional Sciences Faculty Publications

The nuclear receptor PPARα is associated with reducing adiposity, especially in the liver, where it transactivates genes for β-oxidation. Contrarily, the function of PPARα in extrahepatic tissues is less known. Therefore, we established the first adipose-specific PPARα knockout (Ppara^FatKO) mice to determine the signaling position of PPARα in adipose tissue expansion that occurs during the development of obesity. To assess the function of PPARα in adiposity, female and male mice were placed on a high-fat diet (HFD) or normal chow for 30 weeks. Only the male Ppara^FatKO animals had significantly more adiposity in the inguinal white …

Editorial: Recent Advances In Cardiotoxicity Testing, Tamer M. A. Mohamed, Javid Moslehi, Jonathan Satin

Physiology Faculty Publications

No abstract provided.

Gestational Diabetes Triggers Postpartum Cardiac Hypertrophy Via Activation Of Calcineurin/Nfat Signaling, Nirmal Verma, Sarah Srodulski, Sathya Velmurugan, Amanda Hoskins, Vivek K. Pandey, Florin Despa, Sanda Despa

Pharmacology and Nutritional Sciences Faculty Publications

Population-based studies identified an association between a prior pregnancy complicated by gestational diabetes mellitus (GDM) and cardiac hypertrophy and dysfunction later in life. It is however unclear whether GDM initiates this phenotype and what are the underlying mechanisms. We addressed these questions by using female rats that express human amylin (HIP rats) as a GDM model and their wild-type (WT) littermates as the normal pregnancy model. Pregnant and two months postpartum HIP females had increased left-ventricular mass and wall thickness compared to non-pregnant HIP females, which indicates the presence of concentric hypertrophy. These parameters were unchanged in WT females during …

Dysregulation Of Systemic Immunity In Aging And Dementia, Jenny Lutshumba, Barbara S. Nikolajczyk, Adam D. Bachstetter

Pharmacology and Nutritional Sciences Faculty Publications

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks …