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The Role of HIV and Monocytes/Macrophages in Adipose Tissue Biology

Shikuma, Cecilia M. MD; Gangcuangco, Louie Mar A. MD; Killebrew, Deirdre A. PhD; LiButti, Daniel E. BSc; Chow, Dominic C. MD, PhD; Nakamoto, Beau K. MD, PhD; Liang, Chin Yuan MS; Milne, Cris I.P. NP; Ndhlovu, Lishomwa C. MD, PhD; Barbour, Jason D. PhD; Shiramizu, Bruce T. MD; Gerschenson, Mariana PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 February 2014 - Volume 65 - Issue 2 - p 151–159
doi: 10.1097/01.qai.0000435599.27727.6c
Basic and Translational Science

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/106 cells) in circulating peripheral CD14+CD16+ 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 CD14+CD16+ 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.

Departments of Medicine, Cell and Molecular Biology, Tropical Medicine, Medical Microbiology, and Pharmacology, University of Hawaii, Honolulu, HI.

Correspondence to: Cecilia M. Shikuma, MD, Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo St., Biomedical Sciences Building 231, Honolulu, HI 96813 (e-mail: shikuma@hawaii.edu).

The authors have no conflicts of interest to disclose.

Supported by Department of Health and Human Services, National Institutes of Health grants: R01AI068525, R01HL095135, P20MD000173, U54RR026136, and U54MD007584 (C.M.S. and B.T.S.) and P20MD000173 and G12MD007601 (M.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Received August 23, 2013

Accepted August 23, 2013

© 2014 by Lippincott Williams & Wilkins