This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Muscle wasting is a common feature of chronic alcohol consumption and AIDS. Involuntary weight loss10% in an HIV-infected individual is a hallmark of 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. Excess alcohol consumption is associated with a 50% incidence of skeletal muscle myopathy, resulting from decreased muscle protein synthesis and accelerated muscle proteolysis. Effects of alcohol consumption on muscle metabolism appear to be multifactorial. Hypothesis: 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.
Specific Aims : To determine the impact of chronic alcohol administration on the temporal progression of whole body, tissue and molecular alterations in body composition, muscle mass and muscle protein synthesis and breakdown, in SIV-infected rhesus monkeys. This study continues to determine 1) body composition throughout the course of SIV infection in chronically alcohol-administered monkeys and in parallel, the in vivo rates of muscle protein synthesis and breakdown, 2) rate-controlling molecular mechanisms involved in both synthetic (eukaryotic initiation factors, myostatin) and degradation (ubiquitin-proteasome) pathways, and 3) recognized endocrine (IGF-I, GH, insulin & testosterone) nutritional (amino acids) and immune (pro-inflammatory cytokines) modulators of muscle mass. Currently, muscle biopsies and DEXA scanning aid in determining these factors. Results will provide knowledge of how alcohol and SIV, independently and in concert, impair the host's cellular metabolic and synthetic mechanisms involved in regulation of muscle mass. To date, three animals remain on the study. One animal shows no indication of infection or viral load and the remaining two show progressive SAIDS. Funding for eight additional animals has been received which will follow the same experimental design.
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