CHRONIC ALCOHOL & AIDS IMPACT ON MUSCLE WASTING

Tulane University Of Louisiana, New Orleans LA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Muscle wasting is a common feature of chronic alcohol consumption and AIDS. Despite significant improvement in control of HIV-infection using highly active anti-retroviral therapy, AIDS wasting syndrome, with the resulting decline in body cell mass, remains a major cause of morbidity and mortality. We have shown that chronic alcohol administration accelerates progression and exacerbates the severity of muscle wasting associated with simian immunodeficiency virus (SIV) infection by altering the balance between protein anabolic and catabolic mechanisms. This study examines the endocrine and anabolic response to feeding in alcohol-treated animals prior to SIV infection and during the initial asymptomatic phase of infection and the added burden imposed by antiretroviral therapy (ART). Methods: In vivo rates of muscle protein synthesis were determined by percutaneous muscle biopsies following feeding of a nutritionally and calorically controlled diet. Muscle expression of the rate-controlling molecular mechanisms involved in both synthetic (eukaryotic initiation factors, myostatin) and degradation (ubiquitin-proteasome) pathways, and circulating and tissue levels of recognized endocrine (IGF-I, GH, insulin &testosterone) nutritional (amino acids) and immune (pro-inflammatory cytokines) modulators of muscle mass will be measured. Results/Discussion: This study has now been completed utilizing the remaining 8 rhesus macaques. Although there are still some results pending our current findings are in accordance with previous results. We found that SIV infected rhesus monkeys treated with ART had an increased bone osteoblastic activity. This data suggest that chronic alcohol consumption accelerates the detrimental side effects of ART by altering the bone formation and resorption balance which could potentially enhance loss of bone mineral mass thereby decreasing bone density. Our data also reveals that SIV infected rhesus administered alcohol have decreased in testosterone and glucagon like peptide levels following caloric controlled feedings.