The molecular signature of HIV-1-associated lipomatosis reveals differential involvement of brown and beige/brite adipocyte cell lineages
Cereijo, Rubén (Universitat de Barcelona)
Gallego-Escuredo, José Miguel (Universitat de Barcelona)
Moure, Ricardo (Universitat de Barcelona)
Villarroya, Joan (Institut d'Investigació Biomèdica Sant Pau)
Domingo, Joan Carles (Universitat de Barcelona)
Fontdevila, Joan (Hospital Clínic i Provincial de Barcelona)
Martínez, Esteban (Hospital Clínic i Provincial de Barcelona)
Del Mar Gutiérrez, María (Institut d'Investigació Biomèdica Sant Pau)
Mateo, María Gracia (Institut d'Investigació Biomèdica Sant Pau)
Giralt, Marta (Universitat de Barcelona)
Domingo, Pere (Institut d'Investigació Biomèdica Sant Pau)
Villarroya, Francesc (Universitat de Barcelona)
Universitat Autònoma de Barcelona

Data:	2015
Resum:	Highly active antiretroviral therapy has remarkably improved quality of life of HIV-1-infected patients. However, this treatment has been associated with the so-called lipodystrophic syndrome, which conveys a number of adverse metabolic effects and morphological alterations. Among them, lipoatrophy of subcutaneous fat in certain anatomical areas and hypertrophy of visceral depots are the most common. Less frequently, lipomatous enlargements of subcutaneous fat at distinct anatomic areas occur. Lipomatous adipose tissue in the dorso-cervical area ("buffalo hump") has been associated with a partial white-to-brown phenotype transition and with increased cell proliferation, but, to date, lipomatous enlargements arising in other parts of the body have not been characterized. In order to establish the main molecular events associated with the appearance of lipomatosis in HIV-1 patients, we analyzed biopsies of lipomatous tissue from "buffalo hump" and from other anatomical areas in patients, in comparison with healthy subcutaneous adipose tissue, using a marker gene expression approach. Both buffalo-hump and non-buffalo-hump lipomatous adipose tissues exhibited similar patterns of non-compromised adipogenesis, unaltered inflammation, nonfibrotic phenotype and proliferative activity. Shorter telomere length, prelamin A accumulation and SA-β-Gal induction, reminiscent of adipocyte senescence, were also common to both types of lipomatous tissues. Buffalo hump biopsies showed expression of marker genes of brown adipose tissue (e. g. UCP1) and, specifically, of "classical" brown adipocytes (e. g. ZIC1) but not of beige/brite adipocytes. No such brown fat-related gene expression occurred in lipomatous tissues at other anatomical sites. In conclusion, buffalo hump and other subcutaneous adipose tissue enlargements from HIV-1-infected patients share a similar lipomatous character. However, a distorted induction of white-to-"classical brown adipocyte" phenotype appears unique of dorso-cervical lipomatosis. Thus, the insults caused by HIV-1 viral infection and/or antiretroviral therapy leading to lipomatosis are acting in a location- and adipocyte lineage-dependent manner.
Ajuts:	Ministerio de Ciencia e Innovación PI11/02512 Ministerio de Economía y Competitividad PI14/00700 Ministerio de Economía y Competitividad PI14/00063
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Adipocytes, Brown ; Adipocytes, White ; Antiretroviral Therapy, Highly Active ; Cell Lineage ; Female ; Gene Expression ; HIV Infections ; HIV-1 ; Humans ; Ion Channels ; Lipomatosis ; Male ; Middle Aged ; Mitochondrial Proteins ; Subcutaneous Fat ; Transcription Factors ; Uncoupling Protein 1
Publicat a:	PloS one, Vol. 10 Núm. 8 (25 2015) , p. e0136571, ISSN 1932-6203

DOI: 10.1371/journal.pone.0136571
PMID: 26305325

15 p, 1.1 MB

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