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Characterization Of Viral Insulins Reveals White Adipose Tissue Specific Effects In Mice, Martina Chrudinová, Francois Moreau, Hye Lim Noh, Terezie Páníková, Lenka Žáková, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Czech Academy of Sciences, Harvard Medical School, Boston College 2020 Boston College

Characterization Of Viral Insulins Reveals White Adipose Tissue Specific Effects In Mice, Martina Chrudinová, Francois Moreau, Hye Lim Noh, Terezie Páníková, Lenka Žáková, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Czech Academy Of Sciences, Harvard Medical School, Boston College

University of Massachusetts Medical School Faculty Publications

Members of the insulin/IGF superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single chain (sc), i.e. IGF-1-like, forms of the viral insulin/IGF-1 like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e. more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis disease virus-1 ...


Luteinizing Hormone Action In Human Oocyte Maturation And Quality: Signaling Pathways, Regulation, And Clinical Impact, Armando Arroyo, Beomsu Kim, John Yeh 2020 SUNY Upstate Medical University

Luteinizing Hormone Action In Human Oocyte Maturation And Quality: Signaling Pathways, Regulation, And Clinical Impact, Armando Arroyo, Beomsu Kim, John Yeh

Open Access Articles

The ovarian follicle luteinizing hormone (LH) signaling molecules that regulate oocyte meiotic maturation have recently been identified. The LH signal reduces preovulatory follicle cyclic nucleotide levels which releases oocytes from the first meiotic arrest. In the ovarian follicle, the LH signal reduces cyclic nucleotide levels via the CNP/NPR2 system, the EGF/EGF receptor network, and follicle/oocyte gap junctions. In the oocyte, reduced cyclic nucleotide levels activate the maturation promoting factor (MPF). The activated MPF induces chromosome segregation and completion of the first and second meiotic divisions. The purpose of this paper is to present an overview of the ...


Control Of Adipocyte Thermogenesis And Lipogenesis Through Beta3-Adrenergic And Thyroid Hormone Signal Integration, Adilson L. Guilherme, Batuhan Yenilmez, Alexander H. Bedard, Felipe Henriques, Dianxin Liu, Alexandra Lee, Lauren Goldstein, Mark Kelly, Sarah M. Nicoloro, Min Chen, Lee Weinstein, Sheila Collins, Michael P. Czech 2020 University of Massachusetts Medical School

Control Of Adipocyte Thermogenesis And Lipogenesis Through Beta3-Adrenergic And Thyroid Hormone Signal Integration, Adilson L. Guilherme, Batuhan Yenilmez, Alexander H. Bedard, Felipe Henriques, Dianxin Liu, Alexandra Lee, Lauren Goldstein, Mark Kelly, Sarah M. Nicoloro, Min Chen, Lee Weinstein, Sheila Collins, Michael P. Czech

Open Access Articles

Here, we show that beta adrenergic signaling coordinately upregulates de novo lipogenesis (DNL) and thermogenesis in subcutaneous white adipose tissue (sWAT), and both effects are blocked in mice lacking the cAMP-generating G protein-coupled receptor Gs (Adipo-GsalphaKO) in adipocytes. However, UCP1 expression but not DNL activation requires rapamycin-sensitive mTORC1. Furthermore, beta3-adrenergic agonist CL316243 readily upregulates thermogenic but not lipogenic genes in cultured adipocytes, indicating that additional regulators must operate on DNL in sWAT in vivo. We identify one such factor as thyroid hormone T3, which is elevated locally by adrenergic signaling. T3 administration to wild-type mice enhances both thermogenesis and DNL ...


The Role Of Dopamine In Decision Making Processes In Drosophila Melanogaster, Michelle C. Bowers 2020 University of San Diego

The Role Of Dopamine In Decision Making Processes In Drosophila Melanogaster, Michelle C. Bowers

Undergraduate Honors Theses

Understanding the neural processes that mediate decision making is a relatively new field of investigation in the scientific community. With the ultimate goal of understanding how humans decide between one path and another, simpler models such as Drosophila Melanogaster, the common fruit fly, are often utilized as a way of determining the neural circuits involved in these decision-making processes. One of the most important decisions flies make is the decision of where to lay their eggs (oviposit). Choosing the proper substrate upon which to lay eggs is a crucial decision that can ultimately impact their fecundity. This paper investigates the ...


Mechanisms Of Insulin Resistance Related To White, Beige, And Brown Adipocytes, Michael P. Czech 2020 University of Massachusetts Medical School

Mechanisms Of Insulin Resistance Related To White, Beige, And Brown Adipocytes, Michael P. Czech

Open Access Articles

BACKGROUND: The diminished glucose lowering effect of insulin in obesity, called "insulin resistance," is associated with glucose intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses on the molecular and cellular disruptions that contribute to the syndrome. However, significant uncertainty remains on the mechanisms of its initiation and long-term maintenance.

SCOPE OF REVIEW: To simplify insulin resistance analysis, this review focuses on the unifying concept that adipose tissue is a central regulator of systemic glucose homeostasis by controlling liver and skeletal muscle metabolism. Key aspects of adipose function related to insulin resistance ...


Exogenous Gdf11, But Not Gdf8, Reduces Body Weight And Improves Glucose Homeostasis In Mice, Ryan G. Walker, Hye Lim Noh, Taekyoon Kim, Jason K. Kim, Richard T. Lee 2020 Harvard University

Exogenous Gdf11, But Not Gdf8, Reduces Body Weight And Improves Glucose Homeostasis In Mice, Ryan G. Walker, Hye Lim Noh, Taekyoon Kim, Jason K. Kim, Richard T. Lee

Open Access Articles

Insulin resistance is associated with aging in mice and humans. We have previously shown that administration of recombinant GDF11 (rGDF11) to aged mice alters aging phenotypes in the brain, skeletal muscle, and heart. While the closely related protein GDF8 has a role in metabolism, limited data are available on the potential metabolic effects of GDF11 or GDF8 in aging. To determine the metabolic effects of these two ligands, we administered rGDF11 or rGDF8 protein to young or aged mice fed a standard chow diet, short-term high-fat diet (HFD), or long-term HFD. Under nearly all of these diet conditions, administration of ...


Immune-Endocrine Links To Gregariousness In Wild House Mice, Patricia C. Lopes, Esther H. D. Carlitz, Morgan Kindel, Barbara König 2020 Chapman University

Immune-Endocrine Links To Gregariousness In Wild House Mice, Patricia C. Lopes, Esther H. D. Carlitz, Morgan Kindel, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Social interactions are critically important for survival and impact overall-health, but also impose costs on animals, such as exposure to contagious agents. The immune system can play a critical role in modulating social behavior when animals are sick, as has been demonstrated within the context of “sickness behaviors.” Can immune molecules affect or be affected by social interactions even when animals are not sick, therefore serving a role in mediating pathogen exposure? We tested whether markers of immune function in both the blood and the brain are associated with gregariousness, quantified as number of animals interacted with per day. To ...


Recovery Of Viable Endocrine-Specific Cells And Transcriptomes From Human Pancreatic Islet-Engrafted Mice, Sambra D. Redick, Linda Leehy, Ann R. Rittenhouse, David M. Blodgett, Alan G. Derr, Alper Kucukural, Manuel Garber, Leonard D. Shultz, Dale L. Greiner, Jennifer P. Wang, David M. Harlan, Rita Bortell, Agata Jurczyk 2020 University of Massachusetts Medical School

Recovery Of Viable Endocrine-Specific Cells And Transcriptomes From Human Pancreatic Islet-Engrafted Mice, Sambra D. Redick, Linda Leehy, Ann R. Rittenhouse, David M. Blodgett, Alan G. Derr, Alper Kucukural, Manuel Garber, Leonard D. Shultz, Dale L. Greiner, Jennifer P. Wang, David M. Harlan, Rita Bortell, Agata Jurczyk

Program in Molecular Medicine Publications

Human pancreatic islets engrafted into immunodeficient mice serve as an important model for in vivo human diabetes studies. Following engraftment, islet function can be monitored in vivo by measuring circulating glucose and human insulin; however, it will be important to recover viable cells for more complex graft analyses. Moreover, RNA analyses of dissected grafts have not distinguished which hormone-specific cell types contribute to gene expression. We developed a method for recovering live cells suitable for fluorescence-activated cell sorting from human islets engrafted in mice. Although yields of recovered islet cells were relatively low, the ratios of bulk-sorted beta, alpha, and ...


Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer 2020 Arcadia University

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey ...


The Gut-Brain Axis: Assessment Of Ecnl-Dopa In Mice And Dogs, Charlotte Halley 2020 Iowa State University

The Gut-Brain Axis: Assessment Of Ecnl-Dopa In Mice And Dogs, Charlotte Halley

Creative Components

The gut-brain axis is becoming a hot topic in the research world for its possible role in many disorders and diseases. As we take a deeper dive in to its role in neurodegenerative disorders like Parkinson’s disease, we present evidence of a strategy of using genetically engineered probiotic to help regulate and maintain levels of L-DOPA, the gold standard of treatment used in Parkinson’s disease patients. Evidence from trials with mice and dogs present significant findings that prove that a small change like adding a modified E. Coli probiotic may be all the change needed to provide a ...


Intestinal Neurod1 Expression Impairs Paneth Cell Differentiation And Promotes Enteroendocrine Lineage Specification, Joyce H. Li, Subir Ray, Ning Pan, Jody Haigh, Bernd Fritzsch, Andrew B. Leiter 2019 University of Massachusetts Medical School

Intestinal Neurod1 Expression Impairs Paneth Cell Differentiation And Promotes Enteroendocrine Lineage Specification, Joyce H. Li, Subir Ray, Ning Pan, Jody Haigh, Bernd Fritzsch, Andrew B. Leiter

Open Access Articles

Transcription factor Neurod1 is required for enteroendocrine progenitor differentiation and maturation. Several earlier studies indicated that ectopic expression of Neurod1 converted non- neuronal cells into neurons. However, the functional consequence of ectopic Neurod1 expression has not been examined in the GI tract, and it is not known whether Neurod1 can similarly switch cell fates in the intestine. We generated a mouse line that would enable us to conditionally express Neurod1 in intestinal epithelial cells at different stages of differentiation. Forced expression of Neurod1 throughout intestinal epithelium increased the number of EECs as well as the expression of EE specific transcription ...


Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry III, CJ DeLeon, Frank Frisch 2019 Chapman University

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five ...


Use Of Antidiabetic Drugs During Pregnancy Among U.S. Women With Livebirth Deliveries In The Mini-Sentinel System, Katrina Mott, Marsha E. Reichman, Sengwee Toh, Caren Kieswetter, Katherine Haffenreffer, Susan E. Andrade 2019 Harvard University

Use Of Antidiabetic Drugs During Pregnancy Among U.S. Women With Livebirth Deliveries In The Mini-Sentinel System, Katrina Mott, Marsha E. Reichman, Sengwee Toh, Caren Kieswetter, Katherine Haffenreffer, Susan E. Andrade

Open Access Articles

BACKGROUND: As the prevalence of diabetes mellitus increases in the population, the exposure to antidiabetic drugs (ADDs) during pregnancies is expected to grow, as has been seen over the last decade. The objective of this study was to estimate the prevalence of ADD use during pregnancy among women in the Mini-Sentinel Distributed Database (MSDD) who delivered a liveborn infant.

METHODS: We identified qualifying livebirth pregnancies among women aged 10 to 54 years in the MSDD from 2001 to 2013. ADD use was estimated using outpatient pharmacy dispensing claims and days-supplied among three cohorts: all livebirth pregnancies, pregnancies among women with ...


Hormonal Therapy And Preventive Care Of Transgender Patients, Angela Chu, Jana Randolph, Austin Hopkins, Victoria Cho, Sophocles Chrissobolis 2019 Ohio Northern University

Hormonal Therapy And Preventive Care Of Transgender Patients, Angela Chu, Jana Randolph, Austin Hopkins, Victoria Cho, Sophocles Chrissobolis

Pharmacy and Wellness Review

Transgenderism occurs when an individual's gender identity conflicts with the individual's biological sex. A variety of methods may be used in order to reconcile this disparity in transgender individuals including psychological counseling, cross-sex hormone therapy and sex reassignment surgery. The most important role for pharmacists in the treatment of transgender patients is in dispensing hormonal medications for cross-sex treatment. Hormone therapy may be used to suppress characteristics of the patient's biological sex as well as to induce development of characteristics that correlate with the patient's gender identity. In male-to-female (MtF) transgender patients, the most commonly used ...


Expression Of Mitochondrial Membrane-Linked Sab Determines Severity Of Sex-Dependent Acute Liver Injury, Sanda Win, Robert W. M. Min, Christopher Q. Chen, Jun Zhang, Yibu Chen, Meng Li, Ayako Suzuki, Manal F. Abdelmalek, Ying Wang, Mariam Aghajan, Filbert W. M. Aung, Anna Mae Diehl, Roger J. Davis, Tin A. Than, Neil Kaplowitz 2019 University of Southern California

Expression Of Mitochondrial Membrane-Linked Sab Determines Severity Of Sex-Dependent Acute Liver Injury, Sanda Win, Robert W. M. Min, Christopher Q. Chen, Jun Zhang, Yibu Chen, Meng Li, Ayako Suzuki, Manal F. Abdelmalek, Ying Wang, Mariam Aghajan, Filbert W. M. Aung, Anna Mae Diehl, Roger J. Davis, Tin A. Than, Neil Kaplowitz

University of Massachusetts Medical School Faculty Publications

SAB is an outer membrane docking protein for JNK mediated impaired mitochondrial function. Deletion of Sab in hepatocytes inhibits sustained JNK activation and cell death. Current work demonstrated that increasing SAB enhanced the severity of APAP liver injury. Female mice were resistant to liver injury and exhibited markedly decreased hepatic SAB protein expression versus males. The mechanism of SAB repression involved a pathway from ERalpha to p53 expression which induced miR34a-5p. miR34a-5p targeted the Sab mRNA coding region, repressing SAB expression. Fulvestrant or p53 knockdown decreased miR34a-5p and increased SAB in females leading to increased injury from APAP and TNF ...


High-Fat Diet In A Mouse Insulin-Resistant Model Induces Widespread Rewiring Of The Phosphotyrosine Signaling Network, Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Omer H. Yilmaz, Roger J. Davis, Forest M. White 2019 Massachusetts Institute of Technology

High-Fat Diet In A Mouse Insulin-Resistant Model Induces Widespread Rewiring Of The Phosphotyrosine Signaling Network, Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Omer H. Yilmaz, Roger J. Davis, Forest M. White

Open Access Articles

Obesity-associated type 2 diabetes and accompanying diseases have developed into a leading human health risk across industrialized and developing countries. The complex molecular underpinnings of how lipid overload and lipid metabolites lead to the deregulation of metabolic processes are incompletely understood. We assessed hepatic post-translational alterations in response to treatment of cells with saturated and unsaturated free fatty acids and the consumption of a high-fat diet by mice. These data revealed widespread tyrosine phosphorylation changes affecting a large number of enzymes involved in metabolic processes as well as canonical receptor-mediated signal transduction networks. Targeting two of the most prominently affected ...


The Influence Of Different Fat Sources On Steatohepatitis And Fibrosis Development In The Western Diet Mouse Model Of Non-Alcoholic Steatohepatitis (Nash), Hannah K. Drescher, Ralf Weiskirchen, Annabelle Fulop, Carsten Hopf, Estibaliz Gonzalez de San Roman, Pitter F. Huesgen, Alain de Bruin, Laura Bongiovanni, Anette Christ, Rene Tolba, Christian Trautwein, Daniela C. Kroy 2019 University Hospital RWTH Aachen

The Influence Of Different Fat Sources On Steatohepatitis And Fibrosis Development In The Western Diet Mouse Model Of Non-Alcoholic Steatohepatitis (Nash), Hannah K. Drescher, Ralf Weiskirchen, Annabelle Fulop, Carsten Hopf, Estibaliz Gonzalez De San Roman, Pitter F. Huesgen, Alain De Bruin, Laura Bongiovanni, Anette Christ, Rene Tolba, Christian Trautwein, Daniela C. Kroy

Open Access Articles

Non-alcoholic steatohepatitis (NASH) is the leading cause of chronic liver injury and the third most common reason for liver transplantations in Western countries. It is unclear so far how different fat sources in Western diets (WD) influence the development of NASH. Our study investigates the impact of non-trans fat (NTF) and corn oil (Corn) as fat source in a WD mouse model of steatohepatitis on disease development and progression. C57BL/6J wildtype (WT) mice were fed "standard" WD (WD-Std), WD-NTF or WD-Corn for 24 weeks. WT animals treated with WD-NTF exhibit distinct features of the metabolic syndrome compared to WD-Std ...


Testosterone Levels In Men With Chronic Migraine, Lisa B. E. Shields, Tad Seifert, Brent J. Shelton, Brian M. Plato 2019 Norton Healthcare

Testosterone Levels In Men With Chronic Migraine, Lisa B. E. Shields, Tad Seifert, Brent J. Shelton, Brian M. Plato

Markey Cancer Center Faculty Publications

Chronic migraine is a frequent and debilitating condition affecting 14% of the general population. This prospective observational pilot study investigated whether men with chronic migraine have lower than expected total serum testosterone levels. We identified 14 men ages 26-51 at our Institution who fulfilled the ICHD-3b criteria for chronic migraine and obtained serum total testosterone levels. The mean total testosterone level in our 14 patients was 322 ng/dL (range: 120-542 ng/dL) which is in the lower 5% of the reference range for our laboratory (300-1080 ng/dL). Men with chronic migraine had lower total testosterone levels compared to ...


Brown Fat Organogenesis And Maintenance Requires Akt1 And Akt2, Joan Sanchez-Gurmaches, Camila Martinez Calejman, Su Myung Jung, Huawei Li, David A. Guertin 2019 University of Massachusetts Medical School

Brown Fat Organogenesis And Maintenance Requires Akt1 And Akt2, Joan Sanchez-Gurmaches, Camila Martinez Calejman, Su Myung Jung, Huawei Li, David A. Guertin

Open Access Articles

OBJECTIVE: Understanding the signaling mechanisms that control brown adipose tissue (BAT) development is relevant to understanding energy homeostasis and obesity. The AKT kinases are insulin effectors with critical in vivo functions in adipocytes; however, their role in adipocyte development remains poorly understood. The goal of this study was to investigate AKT function in BAT development.

METHODS: We conditionally deleted Akt1 and Akt2 either individually or together with Myf5-Cre, which targets early mesenchymal precursors that give rise to brown adipocytes. Because Myf5-Cre also targets skeletal muscle and some white adipocyte lineages, comparisons were made between AKT function in BAT versus white ...


U.S. Prevalence Of Endocrine Therapy-Naive Locally Advanced Or Metastatic Breast Cancer, Anthony P. Nunes, C. Liang, W. J. Gradishar, T. Dalvi, J. Lewis, N. Jones, E. Green, M. Doherty, J. D. Seeger 2019 University of Massachusetts Medical School

U.S. Prevalence Of Endocrine Therapy-Naive Locally Advanced Or Metastatic Breast Cancer, Anthony P. Nunes, C. Liang, W. J. Gradishar, T. Dalvi, J. Lewis, N. Jones, E. Green, M. Doherty, J. D. Seeger

Open Access Articles

Background: Variations in treatment choice, or late stage at first diagnosis, mean that, despite guideline recommendations, not all patients with hormone receptor (hr)-positive locally advanced or metastatic breast cancer (la/mbca) will have received endocrine therapy before disease progression. In the present study, we aimed to estimate the proportion of women with postmenopausal hr-positive la/mbca in the United States who are endocrine therapy-naive.

Methods: Women in the Optum Electronic Health Record (ehr) database with a breast cancer (bca) diagnosis (January 2008-March 2015) were included. Patient and malignancy characteristics were identified using structured data fields and natural-language processing of ...


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