title: The Molecular Signature of HIV-1-Associated Lipomatosis Reveals Differential Involvement of Brown and Beige/Brite Adipocyte Cell Lineages.
abstract: 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, non-fibrotic 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.
authors: Department of Biochemistry and Molecular Biology, Institute of Biomedicine of the University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain.
authors: Rubén
authors: R
authors: Cereijo
authors: Department of Biochemistry and Molecular Biology, Institute of Biomedicine of the University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain.
authors: José Miguel
authors: JM
authors: Gallego-Escuredo
authors: Department of Biochemistry and Molecular Biology, Institute of Biomedicine of the University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain.
authors: Ricardo
authors: R
authors: Moure
authors: Department of Biochemistry and Molecular Biology, Institute of Biomedicine of the University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain; Infectious Disease Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, and Red de Investigación en SIDA, Instituto de Salud Carlos III, Spain.
authors: Joan
authors: J
authors: Villarroya
authors: Department of Biochemistry and Molecular Biology, Institute of Biomedicine of the University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain.
authors: Joan Carles
authors: JC
authors: Domingo
authors: Department of Plastic Surgery, Hospital Clínic de Barcelona, Barcelona, Catalonia, Spain.
authors: Joan
authors: J
authors: Fontdevila
authors: Infectious Diseases Unit, Faculty of Medicine, University of Barcelona, Hospital Clinic of Barcelona (HCB), Barcelona, Spain.
authors: Esteban
authors: E
authors: Martínez
authors: Infectious Disease Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, and Red de Investigación en SIDA, Instituto de Salud Carlos III, Spain.
authors: Maria del Mar
authors: Mdel M
authors: Gutiérrez
authors: Infectious Disease Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, and Red de Investigación en SIDA, Instituto de Salud Carlos III, Spain.
authors: María Gracia
authors: MG
authors: Mateo
authors: Department of Biochemistry and Molecular Biology, Institute of Biomedicine of the University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain.
authors: Marta
authors: M
authors: Giralt
authors: Infectious Disease Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, and Red de Investigación en SIDA, Instituto de Salud Carlos III, Spain.
authors: Pere
authors: P
authors: Domingo
authors: Department of Biochemistry and Molecular Biology, Institute of Biomedicine of the University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain.
authors: Francesc
authors: F
authors: Villarroya
mesh_terms: D052437:Adipocytes, Brown / Q000473:pathology*; D052438:Adipocytes, White / Q000473:pathology*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D019070:Cell Lineage / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D007473:Ion Channels / Q000096:biosynthesis; D008068:Lipomatosis / Q000150:complications / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D050151:Subcutaneous Fat / Q000473:pathology / Q000821:virology; D014157:Transcription Factors / Q000096:biosynthesis; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; C492123:ZIC1 protein, human