Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Perivascular Adipose Tissue In Relation To Diet, Thermogenesis And Cardiovascular Health, Ginger Paquette, Caitlin Stieber, Ashely Soucy, Benjamin Tero, Lucy Liaw

Thinking Matters Symposium

Adipose tissue is a diverse and crucial component to vascular health due to its role in energy storage and heat production. The primary function of white adipose tissue (WAT) is energy storage while the function of mitochondria-rich brown adipose tissue (BAT) is heat production. Perivascular adipose tissue (PVAT), which surrounds blood vessels, contains both WAT and BAT adipocytes. Dietary calorie restriction is associated with increased lifespan with decreased adiposity. Increased prevalence of WAT-like PVAT, due to high-fat diets and obesity, leads to increased metabolic disfunction and cardiovascular-disease. We used a calorie-restriction model in C57BL6/J mice to test the hypothesis ...

Linking The Brain And Bone Through Fat, Elisabeta Malinici, Anca Sirbu, Miruna Popa, Simona Fica

Journal of Mind and Medical Sciences

Over the past years, bone and adipose tissue have gained interest from researchers in the light of their secretory profiles, being able to produce active molecules, with the final effect of regulating energy homeostasis. Both adipocytes and osteoblasts originate in the pluripotent mesenchymal stem cell and this common origin has been proposed as the core of the fat-bone relationship. The central nervous system might be the third player in this association, capable of integrating signals. Numerous adipose tissue secreted factors that influence energy homeostasis and bone have been described: leptin, adiponectin, lipocalin 2, and inflammatory cytokines (e.g. IL-1, IL-6 ...

Alcohol Consumption And Cognitive Aging: Can It Be Beneficial?, Margarita Velikova, Bistra Galunska, Raya Dimitrova, Zlatislav Stoyanov

Journal of Mind and Medical Sciences

We present a literature review which summarizes the data supporting one of the alternative perspectives on the effect of alcohol consumption on cognitive aging – the possible positive effect of low to moderate drinking. Some of the main theories about aging, the mechanisms of brain aging, and the pathogenesis of cognitive decline and dementia are briefly described. In this context, the putative mechanisms of the protective action of non-alcoholic components in alcoholic beverages or low doses of ethanol against oxidative stress, inflammation, mitochondrial dysfunction, brain insulin resistance, and production of amyloid-β peptides are presented. The review article does not favor the ...

Corruption In Capsules: How It Is Legal For Companies To Put Harmful Ingredients In Vitamins And Dietary Supplements, Emily Leggiero

English Department: Research for Change - Wicked Problems in Our World

The vitamin and supplement industry has increased exponentially in profits as well as potential products on the market since the turn of the century. However, these products are not regulated, nor do they undergo any premarket clinical research or testing. Public health is compromised by vitamins and supplements that are available for American consumption that is disproportionately unregulated to their chemically similar counterparts. This wicked problem is facilitated through the combination of historical legislative definitions that has since been distorted for corrupt administrative gain through the allotment of corporate expenditures. Company disbursements are made to the same policymakers that create ...

Virtualized Clinical Studies To Assess The Natural History And Impact Of Gut Microbiome Modulation In Non-Hospitalized Patients With Mild To Moderate Covid-19 A Randomized, Open-Label, Prospective Study With A Parallel Group Study Evaluating The Physiologic Effects Of Kb109 On Gut Microbiota Structure And Function: A Structured Summary Of A Study Protocol For A Randomized Controlled Study [Preprint], John P. Haran, Jose C. Pinero, Yan Zheng, Norma Alonzo Palma, Mark Wingertzahn

COVID-19 Publications by UMMS Authors

These 2 parallel studies (K031 and K032) aim to evaluate the safety of KB109 in addition to supportive self-care (SSC) compared with SSC alone in outpatients with mild to moderate coronavirus disease 2019 (COVID-19). KB109 is a novel synthetic glycan that was formulated to modulate the gut microbiome composition and metabolic output in order to increase beneficial short-chain fatty acid (SCFA) production in the gut. The K031 study is designed to evaluate the safety of KB109 and characterize its impact on the natural progression of COVID-19 in patients with mild to moderate disease. The K032 study is evaluating the effect ...

Nox4 Mediates Skeletal Muscle Metabolic Responses To Exercise, Kalyn S. Specht, Shashi Kant, Heather Learnard, Maura Campbell, Amada D. Caliz, Yongmei Pei, Michaella M. Reif, John F. Keaney Jr., Siobhan M. Craige

Open Access Publications by UMMS Authors

OBJECTIVE: The immediate signals that couple exercise to metabolic adaptations are incompletely understood. Nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) produces reactive oxygen species (ROS) and plays a significant role in metabolic and vascular adaptation during stress conditions. Our objective was to determine the role of Nox4 in exercise-induced skeletal muscle metabolism.

METHODS: Mice were subjected to acute exercise to assess their immediate responses. mRNA and protein expression responses to Nox4 and hydrogen peroxide (H2O2) were measured by qPCR and immunoblotting. Functional metabolic flux was measured via ex vivo fatty acid and glucose oxidation assays using (14)C-labeled palmitate and ...

Investigation Of Equine In Vivo And In Vitro Derived Metabolites Of The Selective Androgen Receptor Modulator (Sarm) Acp-105 For Improved Doping Control, Malin Nilsson Broberg, Heather Knych, Ulf Bondesson, Curt Pettersson, Scott Stanley, Mario Thevis, Mikael Hedeland

Maxwell H. Gluck Equine Research Center Faculty Publications

Selective Androgen Receptor Modulators (SARMs) have anabolic properties but less adverse effects than anabolic androgenic steroids. They are prohibited in both equine and human sports and there have been several cases of SARMs findings reported over the last few years. The aim of this study was to investigate the metabolite profile of the SARM ACP-105 (2-chloro-4-[(3-endo)-3-hydroxy-3-methyl-8-azabicyclo[3.2.1]oct-8-yl]-3-methylbenzonitrile) in order to find analytical targets for doping control. Oral administration of ACP-105 was performed in horses, where blood and urine samples were collected over a time period of 96 h. The in vivo samples were compared ...

Xylanase Modulates The Microbiota Of Ileal Mucosa And Digesta Of Pigs Fed Corn-Based Arabinoxylans Likely Through Both A Stimbiotic And Prebiotic Mechanism, Amy L. Petry, John F. Patience, Lucas R. Koester, Nichole F. Huntley, Michael R. Bedford, Stephan Schmitz-Esser

Animal Science Publications

The experimental objective was to characterize the impact of insoluble corn-based fiber, xylanase, and an arabinoxylan-oligosaccharide on ileal digesta and mucosa microbiome of pigs. Three replicates of 20 gilts were blocked by initial body weight, individually-housed, and assigned to 1 of 4 dietary treatments: a low-fiber control (LF), a 30% corn bran high-fiber control (HF), HF+100 mg/kg xylanase (HF+XY), and HF+50 mg/kg arabinoxylan oligosaccharide (HF+AX). Gilts were fed their respective treatments for 46 days. On day 46, pigs were euthanized and ileal digesta and mucosa were collected. The V4 region of the 16S rRNA ...

A Feed-Forward Regulatory Loop In Adipose Tissue Promotes Signaling By The Hepatokine Fgf21, Myoung Souk Han, Rachel J. Perry, Joao-Paulo Camporez, Philipp E. Scherer, Gerald I. Shulman, Guangping Gao, Roger J. Davis

University of Massachusetts Medical School Faculty Publications

The cJun NH2-terminal kinase (JNK) signaling pathway is activated by metabolic stress and promotes the development of metabolic syndrome, including hyperglycemia, hyperlipidemia, and insulin resistance. This integrated physiological response involves cross-talk between different organs. Here we demonstrate that JNK signaling in adipocytes causes an increased circulating concentration of the hepatokine fibroblast growth factor 21 (FGF21) that regulates systemic metabolism. The mechanism of organ crosstalk is mediated by a feed-forward regulatory loop caused by JNK-regulated FGF21 autocrine signaling in adipocytes that promotes increased expression of the adipokine adiponectin and subsequent hepatic expression of the hormone FGF21. The mechanism of organ cross-talk ...

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and ...

The Role Of Vascular Endothelial Growth Factor In Leukemia Trafficking, Shaw Powell

Theses and Dissertations--Medical Sciences

Vascular endothelial growth factor (VEGF) is a signaling protein involved in inducing and regulating endothelial cell proliferation and function (Duffy et al 2000). VEGF is also involved in cancer progression, as it induces vascular permeability and promotes angiogenesis to tumor laden areas, giving cancer cells critical oxygen and nutrients (Hoeppner et al.,2012. Studies indicate VEGF prevents lymphoblast apoptosis, which may contribute to leukemia formation and enable the proliferation of leukemic cells (Duffy et al 2000). Ongoing research seeks to further examine VEGF in leukemia, using a rag2:GFP-Myc expressing transgenic zebrafish as the animal model of T-cell Acute Lymphoblastic ...

Neural Stem Cell Metabolic Changes In The Presence Of Interferon-Gamma, Dylan Mckibben

Williams Honors College, Honors Research Projects

Spinal cord injury results in significant disability and health care costs due to an inability of the mature central nervous system to regenerate. One potential therapy would be implantation of neural stem cells to the injury site and stimulation of their differentiation to mature neurons. Previous work has shown that the cytokine interferon-gamma can promote this process; however, the signaling pathways induced in neural stem cells have not been well-defined. This proposal examines neural stem cell metabolic responses to signaling induced by interferon-gamma. Two questions will be answered: i) What specific metabolic pathway is activated to guide neural stem cell ...

Wormpaths: Caenorhabditis Elegans Metabolic Pathway Annotation And Visualization [Preprint], Melissa D. Walker, Gabrielle E. Giese, Amy D. Holdorf, Sushila Bhattacharya, Cedric Diot, Aurian Garcia-Gonzalez, Brent Horowitz, Yong-Uk Lee, Thomas Leland, Xuhang Li, Zeynep Mirza, Huimin Na, Shivani Nanda, Olga Ponomarova, Hefei Zhang, Jingyan Zhang, L. Safak Yilmaz, Albertha J. M. Walhout

University of Massachusetts Medical School Faculty Publications

In our group, we aim to understand metabolism in the nematode Caenorhabditis elegans and its relationships with gene expression, physiology and the response to therapeutic drugs. On March 15, 2020, a stay-at-home order was put into effect in the state of Massachusetts, USA, to flatten the curve of the spread of the novel SARS-CoV2 virus that causes COVID-19. For biomedical researchers in our state, this meant putting a hold on experiments for nine weeks until May 18, 2020. To keep the lab engaged and productive, and to enhance communication and collaboration, we embarked on an in-lab project that we all ...

Preventing Neurodegeneration By Controlling Oxidative Stress: The Role Of Oxr1, Michael R. Volkert, David J. Crowley

Open Access Publications by UMMS Authors

Parkinson's disease, diabetic retinopathy, hyperoxia induced retinopathy, and neuronal damage resulting from ischemia are among the notable neurodegenerative diseases in which oxidative stress occurs shortly before the onset of neurodegeneration. A shared feature of these diseases is the depletion of OXR1 (oxidation resistance 1) gene products shortly before the onset of neurodegeneration. In animal models of these diseases, restoration of OXR1 has been shown to reduce or eliminate the deleterious effects of oxidative stress induced cell death, delay the onset of symptoms, and reduce overall severity. Moreover, increasing OXR1 expression in cells further increases oxidative stress resistance and delays ...

Neutrophil Infiltration Regulates Clock-Gene Expression To Organize Daily Hepatic Metabolism, Maria Crespo, Norman J. Kennedy, Roger J. Davis, Nuria Matesanz, Magdalena Leiva, Guadalupe Sabio

University of Massachusetts Medical School Faculty Publications

Liver metabolism follows diurnal fluctuations through the modulation of molecular clock genes. Disruption of this molecular clock can result in metabolic disease but its potential regulation by immune cells remains unexplored. Here, we demonstrated that in steady state, neutrophils infiltrated the mouse liver following a circadian pattern and regulated hepatocyte clock-genes by neutrophil elastase (NE) secretion. NE signals through c-Jun NH2-terminal kinase (JNK) inhibiting fibroblast growth factor 21 (FGF21) and activating Bmal1 expression in the hepatocyte. Interestingly, mice with neutropenia, defective neutrophil infiltration or lacking elastase were protected against steatosis correlating with lower JNK activation, reduced Bmal1 and increased FGF21 ...

Bifidobacterium Infantis Metabolizes 2'Fucosyllactose-Derived And Free Fucose Through A Common Catabolic Pathway Resulting In 1,2-Propanediol Secretion, Liv R. Dedon, Ezgi Ozcan, Asha Rani, David A. Sela

Open Access Publications by UMMS Authors

Human milk oligosaccharides (HMOs) enrich beneficial bifidobacteria in the infant gut microbiome which produce molecules that impact development and physiology. 2'fucosyllactose (2'FL) is a highly abundant fucosylated HMO which is utilized by Bifidobacterium longum subsp. infantis, despite limited scientific understanding of the underlying mechanism. Moreover, there is not a current consensus on whether free fucose could be metabolized when not incorporated in a larger oligosaccharide structure. Based on metabolic and genomic analyses, we hypothesize that B. infantis catabolizes both free fucose and fucosyl oligosaccharide residues to produce 1,2-propanediol (1,2-PD). Accordingly, systems-level approaches including transcriptomics and proteomics ...

Association Between Circulating Osteocalcin And Cardiometabolic Risk Factors Following A 4-Week Leafy Green Vitamin K-Rich Diet, Alexander Tacey, Marc Sim, Cassandra Smith, Mary N. Woessner, Elizabeth Byrnes, Joshua R. Lewis, Tara Brennan-Speranza, Jonathan M. Hodgson, Lauren C. Blekkenhorst, Itamar Levinger

ECU Publications Post 2013

© 2020 S. Karger AG, Basel. Copyright: All rights reserved. Background: Evidence suggests that lower serum undercarboxylated osteocalcin (ucOC) may be negatively associated with cardiometabolic health. We investigated whether individuals with a suppression of ucOC following an increase in dietary vitamin K1 exhibit a relative worsening of cardiometabolic risk factors. Materials and Methods: Men (n = 20) and women (n = 10) aged 62 ± 10 years participated in a randomized, controlled, crossover study. The primary analysis involved using data obtained from participants following a high vitamin K1 diet (HK; 4-week intervention of increased leafy green vegetable intake). High and low responders were defined ...

Ceramide Analog [18F]F-Hpa-12 Detects Sphingolipid Disbalance In The Brain Of Alzheimer’S Disease Transgenic Mice By Functioning As A Metabolic Probe, Simone M. Crivelli, Daan Van Kruining, Qian Luo, Jo A. A. Stevens, Caterina Giovagnoni, Andreas Paulus, Matthias Bauwens, Dusan Berkes, Helga E. De Vries, Monique T. Mulder, Jochen Walter, Etienne Waelkens, Rita Derua, Johannes V. Swinnen, Jonas Dehairs, Felix M. Mottaghy, Mario Losen, Erhard Bieberich, Pilar Martinez-Martinez

Physiology Faculty Publications

The metabolism of ceramides is deregulated in the brain of Alzheimer’s disease (AD) patients and is associated with apolipoprotein (APO) APOE4 and amyloid-β pathology. However, how the ceramide metabolism changes over time in AD, in vivo, remains unknown. Distribution and metabolism of [¹⁸F]F-HPA-12, a radio-fluorinated version of the ceramide analog N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide, was investigated in the brain of AD transgenic mouse models (FAD) on an APOE4 or APOE3 genetic background, by positron emission tomography and by gamma counter. We found that FAD mice displayed a higher uptake of [¹⁸F]F-HPA-12 in the brain, independently from ...

The Meadow Jumping Mouse Genome And Transcriptome Suggest Mechanisms Of Hibernation [Preprint], Qian Cong, Ethan A. Brem, Jing Zhang, Jessica Alfoldi, Jeremy Johnson, Elinor K. Karlsson, Kerstin Lindblad-Toh, Jason L. Malaney, William J. Israelsen

University of Massachusetts Medical School Faculty Publications

Hibernating mammals exhibit medically relevant phenotypes, but the genetic basis of hibernation remains poorly understood. Using the meadow jumping mouse (Zapus hudsonius), we investigated the genetic underpinnings of hibernation by uniting experimental and comparative genomic approaches. We assembled a Z. hudsonius genome and identified widespread expression changes during hibernation in genes important for circadian rhythm, membrane fluidity, and cell cycle arrest. Tissue-specific gene expression changes during torpor encompassed Wnt signaling in the brain and structural and transport functions in the kidney brush border. Using genomes from the closely related Zapus oregonus (previously classified as Z. princeps) and leveraging a panel ...

Xylanase Supplementation In Corn-Based Swine Diets: A Review With Emphasis On Potential Mechanisms Of Action, Amy L. Petry, John F. Patience

Animal Science Publications

Corn is a common energy source in pig diets globally; when financially warranted, industrial corn coproducts, such as corn distiller’s dried grains with solubles (DDGS), are also employed. The energy provided by corn stems largely from starch, with some contribution from protein, fat, and non-starch polysaccharides (NSP). When corn DDGS are used in the diet, it will reduce starch within the diet; increase dietary protein, fat, and NSP levels; and alter the source profile of dietary energy. Arabinoxylans (AXs) comprise the majority of NSP in corn and its coproducts. One strategy to mitigate the antinutritive effects of NSP and ...