CHRONIC ALCOHOL & AIDS IMPACT ON MUSCLE WASTING

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景：肌肉萎缩是慢性饮酒和艾滋病的共同特征。 尽管使用高效抗逆转录病毒疗法在控制艾滋病毒感染方面取得了重大进展，但艾滋病消耗综合征导致体细胞质量下降，仍然是发病和死亡的主要原因。 我们已经证明，长期饮酒通过改变蛋白质合成代谢和分解代谢机制之间的平衡，加速了与猴免疫缺陷病毒（SIV）感染相关的肌肉萎缩的进展并加剧了其严重程度。 本研究探讨了SIV感染前和感染的初始无症状阶段以及抗逆转录病毒治疗（ART）带来的额外负担期间，酒精处理动物对喂养的内分泌和合成代谢反应。 研究方法：肌肉蛋白质合成的体内速率通过在营养和热量控制的饮食喂养后经皮肌肉活检来确定。 将测量参与合成（真核起始因子、肌肉生长抑制素）和降解（泛素-蛋白酶体）途径的速率控制分子机制的肌肉表达，以及肌肉质量的公认内分泌（IGF-I、GH、胰岛素和睾酮）营养（氨基酸）和免疫（促炎细胞因子）调节剂的循环和组织水平。 结果/讨论：本研究现已使用剩余8只恒河猴完成。 虽然仍有一些结果有待我们目前的研究结果是根据以前的结果。 我们发现SIV感染的恒河猴用ART治疗后骨成骨细胞活性增加。 这些数据表明，长期饮酒通过改变骨形成和再吸收平衡加速ART的有害副作用，这可能会增加骨矿物质量的损失，从而降低骨密度。 我们的数据还显示，SIV感染的恒河猴给予酒精后，在热量控制喂养后，睾酮和胰高血糖素样肽水平下降。

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.