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

Content Provider	Springer Nature : BioMed Central
Author	Mashiko, Takanobu Tsukada, Kunihisa Takada, Hitomi Wu, Szu-Hsien Kanayama, Koji Asahi, Rintaro Mori, Masanori Kurisaki, Akira Oka, Shinichi Yoshimura, Kotaro
Abstract	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.
Related Links	https://aidsrestherapy.biomedcentral.com/counter/pdf/10.1186/s12981-022-00432-9.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	17426405
DOI	10.1186/s12981-022-00432-9
Journal	AIDS Research and Therapy
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2022-03-04
Access Restriction	Open
Subject Keyword	Infectious Diseases Virology Human immunodeficiency virus HIV-associated lipodystrophy Lipoatrophy Gene analysis Adipose-derived stem cell Macrophage
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Virology Pharmacology (medical)
Journal Impact Factor	2.1/2023
5-Year Journal Impact Factor	2.4/2023

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