Chronic alcohol accentuates simian acquired immunodeficiency syndrome-associated wasting

Patricia E. Molina, Charles H. Lang, Margaret McNurlan, Gregory J. Bagby, Steve Nelson

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Background: Survival following human immunodeficiency virus (HIV) infection has improved significantly following the advent of highly active antiretroviral therapy. A large percentage of HIV-infected patients consume and abuse alcohol. Erosion of lean body mass is an important contributing factor to patient morbidity and mortality, and is a common feature of both chronic alcohol (ALC) consumption and acquired immunodeficiency syndrome (AIDS). We hypothesized that alcohol-induced loss in lean body mass is likely to exacerbate the AIDS wasting syndrome, particularly at the terminal stage of AIDS (SAIDS). Methods: This study examined the impact of chronic, intra-gastric ALC (5 h/d × 4 d/wk; blood alcohol levels = 55 mM to 60 mM) administration on body composition and muscle mass in simian immunodeficiency virus (SIV)-infected male Rhesus macaques in contrast to SIV-infected isocaloric (22 kcal/kg/d) sucrose (SUC)-infused control animals at the terminal stage of SIV infection. Results: At terminal stage, ALC/SIV+ animals had significantly lower body weight, body mass index, and limb muscle area than SUC/SIV+ animals. Both ALC/SIV+ and SUC/SIV+ animals had suppressed expression of insulin-like growth factor-I and increased expression of the ubiquitin ligase muscle-specific RING finger-1 mRNA. ALC increased mRNA expression of atrogin-1 (pre-SIV and at SAIDS) and tumor necrosis factor (TNF)-α (SAIDS). These changes were not associated with significant differences in fractional rates of muscle protein synthesis or in overall survival rate. These data show that chronic ALC exacerbated the loss of muscle mass at terminal SAIDS. Conclusion: Our findings suggest the involvement of TNF-α and increased muscle proteolysis via atrogin-1 for the greater erosion of lean body mass at terminal SAIDS in ALC-treated Rhesus macaques.

Original languageEnglish (US)
Pages (from-to)138-147
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume32
Issue number1
DOIs
StatePublished - Jan 2008

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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