Genetic and cytometric analyses of subcutaneous adipose tissue in patients with hemophilia and HIV-associated lipodystrophy.

Autor: Mashiko T; Department of Plastic Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-Shi, Tochigi, 329-0498, Japan.; Department of Plastic Surgery, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan., Tsukada K; AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan., Takada H; Stem Cell Technologies Laboratory, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara, 630-0192, Japan., Wu SH; Department of Plastic Surgery, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan., Kanayama K; Department of Plastic Surgery, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan., Asahi R; Department of Plastic Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-Shi, Tochigi, 329-0498, Japan., Mori M; Department of Plastic Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-Shi, Tochigi, 329-0498, Japan., Kurisaki A; Stem Cell Technologies Laboratory, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara, 630-0192, Japan., Oka S; AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan., Yoshimura K; Department of Plastic Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-Shi, Tochigi, 329-0498, Japan. kotaro-yoshimura@umin.ac.jp.
Jazyk: angličtina
Zdroj: AIDS research and therapy [AIDS Res Ther] 2022 Mar 04; Vol. 19 (1), pp. 14. Date of Electronic Publication: 2022 Mar 04.
DOI: 10.1186/s12981-022-00432-9
Abstrakt: Background: The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients.
Methods: All six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV- healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry.
Results: The time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV.
Conclusions: Our findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes' sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications.
(© 2022. The Author(s).)
Databáze: MEDLINE
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