The role of HIV and monocytes/macrophages in adipose tissue biology.

TitleThe role of HIV and monocytes/macrophages in adipose tissue biology.
Publication TypeJournal Article
Year of Publication2014
AuthorsShikuma CM, Gangcuangco LMar A, Killebrew DA, Libutti DE, Chow DC, Nakamoto BK, Liang CYuan, Milne CIP, Ndhlovu LC, Barbour JD, Shiramizu BT, Gerschenson M
JournalJ Acquir Immune Defic Syndr
Volume65
Issue2
Pagination151-9
Date Published2014 Feb 01
ISSN1944-7884
KeywordsAdipose Tissue, Adult, Cross-Sectional Studies, Female, HIV Infections, HIV-Associated Lipodystrophy Syndrome, Humans, Macrophages, Male, Middle Aged, Monocytes
Abstract

OBJECTIVE: To assess the role of HIV and monocytes/macrophages in adipose tissue dysregulation.

METHODS: Cross-sectional study in 5 groups: HIV seronegative, HIV+ antiretroviral therapy (ART)-naive, HIV+ nonlipoatrophic on zidovudine- and/or stavudine-containing ART, HIV+ lipoatrophic on similar ART, and HIV+ on abacavir- or tenofovir-containing ART. HIV DNA in circulating monocyte subsets was quantitated by real-time polymerase chain reaction. Biopsied subcutaneous fat was examined for macrophage content by CD68 staining. Isolated adipocytes and macrophages were cultured and the supernatant assayed for secretory products by Luminex multiplex cytokine technology.

RESULTS: Sixty-nine subjects were enrolled. Lipoatrophic subjects had higher median HIV DNA levels (270.5 copies/10 cells) in circulating peripheral CD14CD16 co-expressing monocyte subsets compared with subjects who were ART-naive (25.0 copies), nonlipoatrophic (15.0 copies), or on abacavir/tenofovir (57.5 copies), P < 0.01. Group differences in adipocytes and adipose macrophage content were marginal. Although adipocyte secretory products were similar, HIV-infected subjects had higher adipose macrophage-derived interleukin (IL)-12p40, IL-6, IL-8, and monocyte inflammatory protein 1 alpha and lower eotaxin and interferon gamma levels than HIV seronegative subjects (P < 0.05). Within HIV-infected subjects, adipose macrophage secretory products were comparable between subjects naive with ART versus those on ART.

CONCLUSIONS: Circulating HIV-infected and proinflammatory CD14CD16 monocyte subsets contribute to the pathogenesis of HIV-associated lipoatrophy. Among HIV-infected individuals, macrophages, rather than adipocytes, are the primary source of low-grade inflammation in subcutaneous adipose tissue. HIV infection modifies these macrophages to a more proinflammatory phenotype, and these changes are not substantially mitigated by the use of ART.

DOI10.1097/01.qai.0000435599.27727.6c
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID24091690
PubMed Central IDPMC4020346
Grant ListG12 MD007601 / MD / NIMHD NIH HHS / United States
R01AI068525 / AI / NIAID NIH HHS / United States
U54 RR026136 / RR / NCRR NIH HHS / United States
R01 NS053345 / NS / NINDS NIH HHS / United States
P20MD000173 / MD / NIMHD NIH HHS / United States
G12MD007601 / MD / NIMHD NIH HHS / United States
U54RR026136 / RR / NCRR NIH HHS / United States
R01 AI068525 / AI / NIAID NIH HHS / United States
U54MD007584 / MD / NIMHD NIH HHS / United States
R01HL095135 / HL / NHLBI NIH HHS / United States
U54 MD007584 / MD / NIMHD NIH HHS / United States
R01 HL095135 / HL / NHLBI NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
P20 MD000173 / MD / NIMHD NIH HHS / United States
P20 GM103516 / GM / NIGMS NIH HHS / United States