LSUHSC CARC RC2: Alcohol & Metabolic Dysregulation in SIV/HIV; muscle & adipose mechanisms Alcohol use disorders (AUD) are common in people living with HIV/AIDS (PLWHA). Increased survival resulting from antiretroviral therapy (ART), has elevated the risk for comorbid conditions, arising from both chronic alcohol consumption and HIV infection, including myopathy, insulin resistance, prediabetes, and lipodystrophy. Female PLWHA are increasingly reaching and living beyond menopause (occurring at earlier ages) and are afflicted with greater risk for age-associated chronic diseases. Our studies in the chronic binge alcohol (CBA) consuming non-ART simian immunodeficiency virus (SIV)-infected (CBA/SIV) male non-human primates (NHP) showed that decreased and dysfunctional skeletal muscle (SKM) mass is a critical determinant of time to end-stage disease and that acceleration of SAIDS wasting is associated with accentuated SKM inflammation, profound depletion of anti-oxidant capacity, increased proteasome activity, and decreased myoblast differentiation potential. Preliminary findings have identified that CBA/SIV/ART macaques present with lipodystrophy that is reflected in an increased % abdominal adipose tissue deposition, decreased circulating levels of adiponectin, increased adipose tissue inflammatory cytokine and resistin expression, which we hypothesize contributes to decreased insulin sensitivity. The impact of CBA on SIV/ART associated dysregulation of SKM functional phenotype and lipodystrophy, and its interaction with gonadal hormones has not been examined in female NHP. The consequences of ovarian hormone (especially estrogen) loss on metabolic regulation have not been systematically explored in a research or a clinical setting. The proposed studies Alcohol & Metabolic Dysregulation in SIV/HIV; Muscle & Adipose Mechanisms, using a unique experimental approach integrating pre-clinical and clinical in vivo studies with mechanistic in vitro approaches, will be the first to explore the interaction of SKM and adipose tissue in the progression of metabolic dysfunction in CBA/SIV/ART+ female NHP and PLWHA. We hypothesize that SKM and adipose dysfunctional phenotypes will be further accentuated with loss of gonadal function through exacerbation of CBA- and SIV-associated inflammation.
Three Specific Aims test the predictions that dysfunctional SKM phenotype and lipodystrophy precede a detectable decrease in whole body insulin sensitivity, are accentuated by CBA, and further exacerbated by the loss of estrogen following ovariectomy (OVX). Clinical studies will examine whether the incidence of decreased lean body mass, muscle strength, lipodystrophy, and prediabetes are more frequent in female PLWHA with AUD, and accentuated post- menopause. The expected results will have a profound impact on the identification of the underlying mechanisms of CBA (or AUD)-associated insulin resistance in SIV/HIV subjects and the impact of estrogen loss on their severity. Furthermore, they will identify possible targets for therapeutic interventions to ameliorate HIV/ART associated metabolic derangements.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA009803-25
Application #
9386713
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
25
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Type
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Ford Jr, Stephen M; Simon Peter, Liz; Berner, Paul et al. (2018) Differential contribution of chronic binge alcohol and antiretroviral therapy to metabolic dysregulation in SIV-infected male macaques. Am J Physiol Endocrinol Metab :
Boule, Lisbeth A; Ju, Cynthia; Agudelo, Marisela et al. (2018) Summary of the 2016 Alcohol and Immunology Research Interest Group (AIRIG) meeting. Alcohol 66:35-43
Glick, Jennifer L; Andrinopoulos, Katherine M; Theall, Katherine P et al. (2018) ""Tiptoeing Around the System"": Alternative Healthcare Navigation Among Gender Minorities in New Orleans. Transgend Health 3:118-126
Glick, Jennifer L; Theall, Katherine; Andrinopoulos, Katherine et al. (2018) For data's sake: dilemmas in the measurement of gender minorities. Cult Health Sex :1-16
Theall, Katherine P; Felker-Kantor, Erica; Wallace, Maeve et al. (2018) Considering high alcohol and violence neighborhood context using daily diaries and GPS: A pilot study among people living with HIV. Drug Alcohol Depend 187:236-241
Simon, Liz; Siggins, Robert; Winsauer, Peter et al. (2018) Simian Immunodeficiency Virus Infection Increases Blood Ethanol Concentration Duration After Both Acute and Chronic Administration. AIDS Res Hum Retroviruses 34:178-184
Samuelson, Derrick R; Burnham, Ellen L; Maffei, Vincent J et al. (2018) The respiratory tract microbial biogeography in alcohol use disorder. Am J Physiol Lung Cell Mol Physiol 314:L107-L117
Glick, Jennifer L; Theall, Katherine P; Andrinopoulos, Katherine M et al. (2018) The Role of Discrimination in Care Postponement Among Trans-Feminine Individuals in the U.S. National Transgender Discrimination Survey. LGBT Health 5:171-179
Molina, Patricia E; Nelson, Steve (2018) Binge Drinking's Effects on the Body. Alcohol Res 39:99-109
Molina, Patricia E; Simon, Liz; Amedee, Angela M et al. (2018) Impact of Alcohol on HIV Disease Pathogenesis, Comorbidities and Aging: Integrating Preclinical and Clinical Findings. Alcohol Alcohol 53:439-447

Showing the most recent 10 out of 114 publications