Regulation of adiponectin in adipocytes upon exposure to HIV-1.
OBJECTIVE
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.


METHODS
Human subcutaneous preadipocytes and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was measured in supernatants and cell lysates.


RESULTS
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.


CONCLUSIONS
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.
Sankalé
J-L G
JL
Department of Immunology & Infectious Diseases and Harvard AIDS Institute, Harvard School of Public Health, Boston, MA, USA.
Tong
Q
Q
Hadigan
C M
CM
Tan
G
G
Grinspoon
S K
SK
Kanki
P J
PJ
Hotamisligil
G S
GS
D017667:Adipocytes / Q000502:physiology* / Q000821:virology; D050156:Adipogenesis / Q000502:physiology; D052242:Adiponectin / Q000032:analysis / Q000502:physiology*; D000273:Adipose Tissue / Q000737:chemistry / Q000821:virology; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D015658:HIV Infections / Q000175:diagnosis; D015497:HIV-1 / Q000472:pathogenicity*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000503:physiopathology / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000502:physiology / Q000821:virology; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D015728:Receptors, HIV / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D052242:Adiponectin; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D015728:Receptors, HIV; D014409:Tumor Necrosis Factor-alpha