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Chronic binge alcohol in SIV infection: impact of adipose tissue stiffness on metabolic dysfunction

SIV 感染中的慢性酗酒：脂肪组织硬度对代谢功能障碍的影响

基本信息

批准号：
10013606
负责人：
Jonquil M Poret
金额：
$ 3.74万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10013606
关键词：
AIDS/HIV problem Actins Adipocytes Adipose tissue Alcohol consumption Alcohols Animal Model Cell Adhesion Molecules Cell Communication Cell Size Cells Chronic Collagen Collagen Fiber Communication Complement Critical Thinking Deposition Development Disintegrins Elastin Elastin Fiber Environment Enzymes Experimental Designs Extracellular Matrix Extracellular Matrix Proteins Fatty acid glycerol esters Fellowship Fibrillar Collagen Fibronectins Foundations Functional disorder Funding Future General Population Genes Glycoproteins Goals HIV Health Sciences Homeostasis Impairment In Vitro Infiltration Inflammatory Influentials Insulin Laboratories Leadership Lipolysis Literature Liver Louisiana Macaca Macaca mulatta Matrix Metalloproteinase Inhibitor Matrix Metalloproteinases Mediating Mentors Mentorship Metabolic Metabolic dysfunction Metabolism Metalloproteases Modeling Molecular National Institute on Alcohol Abuse and Alcoholism National Research Service Awards Oral Pathology Pathway Analysis Pathway interactions Persons Physiology Plasminogen Activator Inhibitor 1 Pre-Clinical Model Protein-Lysine 6-Oxidase Proteoglycan Reporting Research Research Design Research Personnel Research Training Resources SIV Scientist Signal Transduction Skeletal Muscle Stains Structure Techniques Testing Tissues Training Universities Virus Diseases Work alcohol effect alcohol misuse alcohol research alcohol risk alcohol use disorder antiretroviral therapy career cell type comorbidity crosslink culture plates design glucose uptake in vivo lipid biosynthesis male polydimethylsiloxane pre-clinical pre-doctoral simian human immunodeficiency virus skills stem cell differentiation stem cells success tissue injury training opportunity translational study

项目摘要

ABSTRACT The goal of this Ruth L. Kirschstein NRSA F31-Diversity application is to enhance the predoctoral training of a young future alcohol researcher. This fellowship opportunity will also provide the applicant with research training required to conduct High Priority HIV/AIDS-related research. The applicant will achieve skills to conduct research concentrated on alcohol-mediated metabolic dysfunction in the highly relevant preclinical model of chronic binge alcohol (CBA) and simian immunodeficiency virus (SIV) infection. At-risk alcohol use among people living with HIV (PLWH) is nearly twice that of the general population. Also, chronic at-risk alcohol use and HIV/SIV are both independently associated with tissue injury, including adipose tissue injury. Previous work from our laboratory using a SIV model indicates that CBA administration decreases differentiation of adipose derived stem cells (ADSC), decreased adipocyte cell size and increases collagen deposition and inflammatory cell infiltration in asymptomatic male macaques. However, to our knowledge, there have been no previous studies to investigate the impact of CBA-induced adipose tissue stiffness on adipocyte metabolic capacity and function in the context of SIV/HIV. Reports in the scientific literature and our previous studies support the central hypothesis that CBA- induced omental adipose tissue (OmAT) stiffness is mediated by dysregulation of extracellular matrix (ECM) composition promoting adipocyte metabolic dysregulation in SIV+ rhesus macaques. The proposed studies to be performed as part of the applicant’s training plan will utilize an integrated approach to assess the following Specific Aims: 1) Test the hypothesis that CBA-mediated OmAT pro-fibrotic milieu results from an imbalance in ECM synthesis and degradation in SIV-infected macaques and 2) Test the hypothesis that fibrotic ECM decreases metabolic capacity of ADSCs isolated from SIV-infected macaques. Findings from the proposed studies will provide a more comprehensive understanding adipose tissue dysfunction in the context of SIV and alcohol and will provide the foundation for future translational studies. Completion of the proposed research and training will facilitate the applicant’s progression to an independent researcher in the field of alcohol-induced metabolic dysregulation.

摘要