|Sankale, J-Lg - HARVARD SPH|
|Hadigan, C - HARVARD MEDICAL SCHOOL|
|Tan, G - HARVARD SPH|
|Grinspoon, S - HARVARD MEDICAL SCHOOL|
|Kankil, P - HARVARD SPH|
|Hotamisligil, G - HARVARD SPH|
Submitted to: HIV Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 19, 2005
Publication Date: May 20, 2006
Citation: Sankale, J., Tong, Q., Hadigan, C.M., Tan, G., Grinspoon, S.K., Kankil, P.J., Hotamisligil, G.S. 2006. Regulation of adiponectin in adipocytes upon exposure to HIV-1. HIV Medicine. 7(4):268-274. Interpretive Summary: In this paper, we reported our finding that human fat cells also have receptors for the HIV virus. However, HIV virus can not infect human fat cell. Even though HIV virus could not enter and replicate in human fat cells, the HIV viruses do affect the function of human fat cells, for instance, the secretion of adiponectin, an important hormone regulating insulin action and metabolism.
Technical Abstract: Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose peptide implicated in regulation of glucose and lipid metabolisms. In this study we investigated the effect of HIV on adipocytes, to determine whether HIV can directly infect adipocytes and/or alter the regulation and secretion of the adipocyte-derived hormone adiponectin. Human subcutaneous preadipocytes and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was measured in supernatants and cell lysates. Although adipocytes expressed CD4, the major HIV receptor, they could not be infected in vitro. However, exposure to HIV dramatically increased the secretion of adiponectin from human adipocytes, in the absence of infection. This was exacerbated with sustained exposure to HIV in a transwell assay. Further, human peripheral mononuclear cells also produced adiponectin, but this was largely dependent upon T-cell activation. We propose that the stimulation of adiponectin production by HIV can perturb adiponectin regulation, leading to substantially decreased levels upon viral suppression by antiretroviral therapy. These data suggest a potential molecular mechanism of adiponectin regulation in HIV-infected patients.