HIV lipoatrophy, the wasting of subcutaneous adipose tissue, is part of the metabolic syndrome in 50-70% of patients on highly active antiretroviral therapy (HAART). Lipoatrophy leads to social stigma that can inhibit a patient from adhering to the prescribed medication schedule. We have shown that one of the causes of HIV lipoatrophy is mitochondrial dysfunction due to the HIV drugs, nucleoside reverse transcriptase inhibitors (NRTIs). Additionally, the role of inflammation has been suggested in the literature to influence the development of lipoatrophy. An increase in proinflammatory cytokines has been found in HIV positive patients, as well as those diagnosed with lipodystrophy. However, the etiology of the origin of this cytokine production has yet to be elucidated. Our hypothesis is that peripheral blood macrophages (MDMs), activated by HIV-1, infiltrate adipose tissue and produce pro-inflammatory cytokines. This chronic inflammation caused by MDMs amplifies the mitochondrial dysfunction and oxidative stress induced in adipose tissue by antiretroviral medications. We will examine immunological and mitochondrial parameters in MDMs and gluteal fat biopsies cells from Lipoatrophic (HIV+) (n=15), Non-Lipoatrophic (HIV+) (n=15), NTRI naive (HIV+) (n=15), and HIV negative participants (n=15). We will isolate adipocytes and a preadipocytes fraction (with the macrophages) from the fat biopsies and assess for: macrophages by CD68 expression, cytokine expression, mtDNA copies/cell, and RNA and protein expression of mitochondrial oxidative phosphorylation. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL085025-02
Application #
7232646
Study Section
Special Emphasis Panel (ZRG1-AARR-B (03))
Program Officer
Mondoro, Traci
Project Start
2006-05-01
Project End
2007-12-31
Budget Start
2007-05-01
Budget End
2007-12-31
Support Year
2
Fiscal Year
2007
Total Cost
$41,796
Indirect Cost
Name
University of Hawaii
Department
Other Clinical Sciences
Type
Schools of Medicine
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822