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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 protein for various marker genes in BH and non-BH lipomas from HIV-1–infected, HAART-treated patients and healthy control subcutaneous adipose tissue.A) Relative protein levels of the indicated markers of adipogenesis and adipocyte function, mitochondrial function, inflammation, and cell proliferation were determined by densitometric analysis of Western blots. Means ± SEM of 10 (C, BH) and 8 (NBL) samples expressed as ratios of the optical density of each band corrected for total protein level, are shown for each protein (*p<0.05, **p<0.01 and, lipomas vs. healthy subcutaneous adipose tissue; #p<0.05, ##p<0.01 and ###p<0.001, NBL vs. BH). B) Representative Western blot bands for selected genes of each functional group in panel A for controls (C), BH, and NBL. Each sample corresponds to an individual from each group. β-actin was used a loading control. The molecular weight of each specific immunoreactive signal is shown at right. ADIPOQ, adiponectin; MT_COII, mitochondrial DNA-encoded subunit II of cytochrome c oxidase.
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pone.0136571.g002: Expression of protein for various marker genes in BH and non-BH lipomas from HIV-1–infected, HAART-treated patients and healthy control subcutaneous adipose tissue.A) Relative protein levels of the indicated markers of adipogenesis and adipocyte function, mitochondrial function, inflammation, and cell proliferation were determined by densitometric analysis of Western blots. Means ± SEM of 10 (C, BH) and 8 (NBL) samples expressed as ratios of the optical density of each band corrected for total protein level, are shown for each protein (*p<0.05, **p<0.01 and, lipomas vs. healthy subcutaneous adipose tissue; #p<0.05, ##p<0.01 and ###p<0.001, NBL vs. BH). B) Representative Western blot bands for selected genes of each functional group in panel A for controls (C), BH, and NBL. Each sample corresponds to an individual from each group. β-actin was used a loading control. The molecular weight of each specific immunoreactive signal is shown at right. ADIPOQ, adiponectin; MT_COII, mitochondrial DNA-encoded subunit II of cytochrome c oxidase.

Mentions: We next extended our study to an analysis of marker expression at the protein level (Fig 2A and 2B). Unlike transcripts, protein levels of PPARγ, LPL and adiponectin as well as those of the glucose transporter GLUT4, another protein associated with adipogenesis, were not significantly different between BH or NBL samples and controls. The abundance of β2-microglobulin, an indicator of inflammation, was also unaltered. Levels of the mtDNA-encoded protein MT-CO2 were significantly reduced relative to controls to a similar extent in both BH and NBL samples. An analysis of the expression of the proliferation marker, PCNA [26], showed a substantial increase in PCNA protein levels in BH and NBL relative to healthy subcutaneous adipose tissue, with the extent of the increase being similar for the two types of lipomatous tissue.


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 protein for various marker genes in BH and non-BH lipomas from HIV-1–infected, HAART-treated patients and healthy control subcutaneous adipose tissue.A) Relative protein levels of the indicated markers of adipogenesis and adipocyte function, mitochondrial function, inflammation, and cell proliferation were determined by densitometric analysis of Western blots. Means ± SEM of 10 (C, BH) and 8 (NBL) samples expressed as ratios of the optical density of each band corrected for total protein level, are shown for each protein (*p<0.05, **p<0.01 and, lipomas vs. healthy subcutaneous adipose tissue; #p<0.05, ##p<0.01 and ###p<0.001, NBL vs. BH). B) Representative Western blot bands for selected genes of each functional group in panel A for controls (C), BH, and NBL. Each sample corresponds to an individual from each group. β-actin was used a loading control. The molecular weight of each specific immunoreactive signal is shown at right. ADIPOQ, adiponectin; MT_COII, mitochondrial DNA-encoded subunit II of cytochrome c oxidase.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4549259&req=5

pone.0136571.g002: Expression of protein for various marker genes in BH and non-BH lipomas from HIV-1–infected, HAART-treated patients and healthy control subcutaneous adipose tissue.A) Relative protein levels of the indicated markers of adipogenesis and adipocyte function, mitochondrial function, inflammation, and cell proliferation were determined by densitometric analysis of Western blots. Means ± SEM of 10 (C, BH) and 8 (NBL) samples expressed as ratios of the optical density of each band corrected for total protein level, are shown for each protein (*p<0.05, **p<0.01 and, lipomas vs. healthy subcutaneous adipose tissue; #p<0.05, ##p<0.01 and ###p<0.001, NBL vs. BH). B) Representative Western blot bands for selected genes of each functional group in panel A for controls (C), BH, and NBL. Each sample corresponds to an individual from each group. β-actin was used a loading control. The molecular weight of each specific immunoreactive signal is shown at right. ADIPOQ, adiponectin; MT_COII, mitochondrial DNA-encoded subunit II of cytochrome c oxidase.
Mentions: We next extended our study to an analysis of marker expression at the protein level (Fig 2A and 2B). Unlike transcripts, protein levels of PPARγ, LPL and adiponectin as well as those of the glucose transporter GLUT4, another protein associated with adipogenesis, were not significantly different between BH or NBL samples and controls. The abundance of β2-microglobulin, an indicator of inflammation, was also unaltered. Levels of the mtDNA-encoded protein MT-CO2 were significantly reduced relative to controls to a similar extent in both BH and NBL samples. An analysis of the expression of the proliferation marker, PCNA [26], showed a substantial increase in PCNA protein levels in BH and NBL relative to healthy subcutaneous adipose tissue, with the extent of the increase being similar for the two types of lipomatous tissue.

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