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.Background: Muscle wasting is a common feature of chronic alcohol consumption and AIDS with involuntary weight loss 10% being 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 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 will examine the endocrine and anabolic response to feeding in alcohol-treated animals prior to SIV infection and during the initial asymptomatic phase of infection. Studies will involve measurements of in vivo rates of muscle protein synthesis following feeding of a nutritionally and calorically controlled diet. 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. Eight, uninfected animals who have reached the end of baseline alcohol administration remain in the study. Results: Results from our completed studies showed that chronic alcohol/SIV+ animals showed higher viral load at 3 months post-SIV infection as well as a significant and early decrease in caloric intake and nitrogen balance associated with a change in food choice. Muscle TNF- mRNA expression was markedly increased at 10 months post-SIV infection in alcohol/SIV+ animals. At terminal stage, ALC/SIV+ animals had significantly lower body weight, body mass index, and limb muscle area than SUC/SIV+ animals. These data show that chronic ALC exacerbates loss of muscle mass at terminal SAIDS. Our findings suggest the involvement of TNF and increased muscle proteolysis via atrogin-1 for the greater erosion of lean body mass at terminal SAIDS in chronic alcohol-treated Rhesus macaques.
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