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The Molecular Signature of HIV-1-Associated Lipomatosis Reveals Differential Involvement of Brown and Beige/Brite Adipocyte Cell Lineages.

Cereijo R, Gallego-Escuredo JM, Moure R, Villarroya J, Domingo JC, Fontdevila J, Martínez E, Gutiérrez Mdel M, Mateo MG, Giralt M, Domingo P, Villarroya F - PLoS ONE (2015)

Bottom Line: However, this treatment has been associated with the so-called lipodystrophic syndrome, which conveys a number of adverse metabolic effects and morphological alterations.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.However, a distorted induction of white-to-"classical brown adipocyte" phenotype appears unique of dorso-cervical lipomatosis.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Expression of mRNA for various marker genes and mtDNA levels in BH and non-BH lipomas from HIV-1–infected, HAART-treated patients and healthy control subcutaneous adipose tissue.A) Relative mRNA levels of the indicated markers of adipogenesis and adipocyte function, mitochondrial function, inflammation, and fibrosis were determined by qRT-PCR. Means ± SEM, expressed as ratios relative to 18S rRNA, are shown for each target mRNA. B) mtDNA data are presented as means ± SEM, expressed as a ratio units between the mitochondrial gene MT CYB and the single-copy nuclear gene CEBPA levels (*p<0.05, lipomas vs. healthy control; #p<0.05, NBL vs. BH). (*p<0.05, **p<0.01 and ***p<0.001, lipoma vs. healthy subcutaneous adipose tissue; #p<0.05, ##p<0.01, NBL vs BH). Means correspond to 10 (C, BH) and 8 (NBL) samples.
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pone.0136571.g001: Expression of mRNA for various marker genes and mtDNA levels in BH and non-BH lipomas from HIV-1–infected, HAART-treated patients and healthy control subcutaneous adipose tissue.A) Relative mRNA levels of the indicated markers of adipogenesis and adipocyte function, mitochondrial function, inflammation, and fibrosis were determined by qRT-PCR. Means ± SEM, expressed as ratios relative to 18S rRNA, are shown for each target mRNA. B) mtDNA data are presented as means ± SEM, expressed as a ratio units between the mitochondrial gene MT CYB and the single-copy nuclear gene CEBPA levels (*p<0.05, lipomas vs. healthy control; #p<0.05, NBL vs. BH). (*p<0.05, **p<0.01 and ***p<0.001, lipoma vs. healthy subcutaneous adipose tissue; #p<0.05, ##p<0.01, NBL vs BH). Means correspond to 10 (C, BH) and 8 (NBL) samples.

Mentions: The levels of transcripts for marker genes related to adipogenesis and adipose function (PPAR-γ, LPL and AdipoQ), inflammation (TNFα), macrophage infiltration (CD68), mitochondrial toxicity (MT-CO2), and fibrosis (COL1A2) were determined in lipomatous and healthy control adipose tissues (Fig 1). Lipomatous adipose tissue data were analyzed separately for BH samples and non-BH lipomatous tissue (NBL), as described in Materials and Methods.


The Molecular Signature of HIV-1-Associated Lipomatosis Reveals Differential Involvement of Brown and Beige/Brite Adipocyte Cell Lineages.

Cereijo R, Gallego-Escuredo JM, Moure R, Villarroya J, Domingo JC, Fontdevila J, Martínez E, Gutiérrez Mdel M, Mateo MG, Giralt M, Domingo P, Villarroya F - PLoS ONE (2015)

Expression of mRNA for various marker genes and mtDNA levels in BH and non-BH lipomas from HIV-1–infected, HAART-treated patients and healthy control subcutaneous adipose tissue.A) Relative mRNA levels of the indicated markers of adipogenesis and adipocyte function, mitochondrial function, inflammation, and fibrosis were determined by qRT-PCR. Means ± SEM, expressed as ratios relative to 18S rRNA, are shown for each target mRNA. B) mtDNA data are presented as means ± SEM, expressed as a ratio units between the mitochondrial gene MT CYB and the single-copy nuclear gene CEBPA levels (*p<0.05, lipomas vs. healthy control; #p<0.05, NBL vs. BH). (*p<0.05, **p<0.01 and ***p<0.001, lipoma vs. healthy subcutaneous adipose tissue; #p<0.05, ##p<0.01, NBL vs BH). Means correspond to 10 (C, BH) and 8 (NBL) samples.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4549259&req=5

pone.0136571.g001: Expression of mRNA for various marker genes and mtDNA levels in BH and non-BH lipomas from HIV-1–infected, HAART-treated patients and healthy control subcutaneous adipose tissue.A) Relative mRNA levels of the indicated markers of adipogenesis and adipocyte function, mitochondrial function, inflammation, and fibrosis were determined by qRT-PCR. Means ± SEM, expressed as ratios relative to 18S rRNA, are shown for each target mRNA. B) mtDNA data are presented as means ± SEM, expressed as a ratio units between the mitochondrial gene MT CYB and the single-copy nuclear gene CEBPA levels (*p<0.05, lipomas vs. healthy control; #p<0.05, NBL vs. BH). (*p<0.05, **p<0.01 and ***p<0.001, lipoma vs. healthy subcutaneous adipose tissue; #p<0.05, ##p<0.01, NBL vs BH). Means correspond to 10 (C, BH) and 8 (NBL) samples.
Mentions: The levels of transcripts for marker genes related to adipogenesis and adipose function (PPAR-γ, LPL and AdipoQ), inflammation (TNFα), macrophage infiltration (CD68), mitochondrial toxicity (MT-CO2), and fibrosis (COL1A2) were determined in lipomatous and healthy control adipose tissues (Fig 1). Lipomatous adipose tissue data were analyzed separately for BH samples and non-BH lipomatous tissue (NBL), as described in Materials and Methods.

Bottom Line: However, this treatment has been associated with the so-called lipodystrophic syndrome, which conveys a number of adverse metabolic effects and morphological alterations.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.However, a distorted induction of white-to-"classical brown adipocyte" phenotype appears unique of dorso-cervical lipomatosis.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus