Background: Separately, chronic alcohol ingestion and HIV-1 infection are associated with severe skeletal muscle\r\nderangements, including atrophy and wasting, weakness, and fatigue. One prospective cohort study reported that\r\n41% of HIV-infected patients met the criteria for alcoholism, however; few reports exist on the co-morbid effects of\r\nthese two disease processes on skeletal muscle homeostasis. Thus, we analyzed the atrophic effects of chronic\r\nalcohol ingestion in HIV-1 transgenic rats and identified alterations to several catabolic and anabolic factors.\r\nFindings: Relative plantaris mass, total protein content, and fiber cross-sectional area were reduced in each\r\nexperimental group compared to healthy, control-fed rats. Alcohol abuse further reduced plantaris fiber area in\r\nHIV-1 transgenic rats. Consistent with previous reports, gene levels of myostatin and its receptor activin IIB were\r\nnot increased in HIV-1 transgenic rat muscle. However, myostatin and activin IIB were induced in healthy and HIV-1\r\ntransgenic rats fed alcohol for 12 weeks. Catabolic signaling factors such as TGFb1, TNFa, and phospho-p38/totalp38\r\nwere increased in all groups compared to controls. There was no effect on IL-6, leukemia inhibitory factor (LIF),\r\ncardiotrophin-1 (CT-1), or ciliary neurotrophic factor (CNTF) in control-fed, transgenic rats. However, the comorbidity\r\nof chronic alcohol abuse and HIV-1-related protein expression decreased expression of the two anabolic\r\nfactors, CT-1 and CNTF.\r\nConclusions: Consistent with previous reports, alcohol abuse accentuated skeletal muscle atrophy in an animal\r\nmodel of HIV/AIDS. While some catabolic pathways known to drive alcoholic or HIV-1-associated myopathies were\r\nalso elevated in this co-morbid model (e.g., TGFb1), consistent expression patterns were not apparent. Thus, specific\r\nalterations to signaling mechanisms such as the induction of the myostatin/activin IIB system or reductions in\r\ngrowth factor signaling via CT-1- and CNTF-dependent mechanisms may play larger roles in the regulation of\r\nmuscle mass in alcoholic, HIV-1 models.
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