Similarity of mouse perivascular and brown adipose tissue and their resitance to diet-induced inflammation

Program in Molecular Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
AJP Heart and Circulatory Physiology (Impact Factor: 3.84). 07/2011; 301(4):H1425-37. DOI: 10.1152/ajpheart.00376.2011
Source: PubMed


Thoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and the metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually identical to BAT, with equally high expression of Ucp-1, Cidea, and other genes known to be uniquely or very highly expressed in BAT. PVAT and BAT also displayed nearly identical phenotypes upon immunohistochemical analysis, and electron microscopy confirmed that PVAT contained multilocular lipid droplets and abundant mitochondria. Compared with white adipose tissue (WAT), PVAT and BAT from C57BL6/J mice fed a high-fat diet for 13 wk had markedly lower expression of immune cell-enriched mRNAs, suggesting resistance to obesity-induced inflammation. Indeed, staining of BAT and PVAT for macrophage markers (F4/80 and CD68) in obese mice showed virtually no macrophage infiltration, and FACS analysis of BAT confirmed the presence of very few CD11b(+)/CD11c(+) macrophages in BAT (1.0%) compared with WAT (31%). In summary, murine PVAT from the thoracic aorta is virtually identical to interscapular BAT, is resistant to diet-induced macrophage infiltration, and thus may play an important role in protecting the vascular bed from inflammatory stress.

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    • "Psgl-1 deficiency prevented PVAT inflammation and endothelial dysfunction [57]. In contrast to the abovementioned findings, Fitzgibbons et al. [58] have proposed that mice thoracic PVAT shows a very low inflammation after 13 wk of HFD, probably due to its similarity with the brown adipose tissue phenotype. This study suggests the attractive possibility of promoting a BAT phenotype in PVAT which might have preventive effects in vascular disease development. "
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    ABSTRACT: Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT) was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important number of adipocyte-derived factors with physiological and pathophysiological paracrine vasoactive effects have been identified. PVAT undergoes structural and functional changes in obesity. During early diet-induced obesity, an adaptative overproduction of vasodilator factors occurs in PVAT, probably aimed at protecting vascular function. However, in established obesity, PVAT loses its anticontractile properties by an increase of contractile, oxidative, and inflammatory factors, leading to endothelial dysfunction and vascular disease. The aim of this review is to focus on PVAT dysfunction mechanisms in obesity.
    International Journal of Endocrinology 11/2013; 2013:402053. DOI:10.1155/2013/402053 · 1.95 Impact Factor
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    • "PVAT differs substantially from other fat depots with respect to its secretory profile. For example, mouse aortic PVAT produces less adiponectin, leptin, and resistin, expresses lower levels of lipid-oxidation genes, and has the reverse expression profile of adipose-related and lipid synthesis and storage genes compared with SAT and VAT.3,4 Comparatively, transcriptome analyses have shown there are far less differences in gene expression between murine aortic PVAT and interscapullary BAT, nominally only a total of 228 genes, while registering similar expression levels for classically brown adipocyte-enriched genes, such as UCP-1 and Cidea.3 The secretory profile is not the only characteristic distinguishing the PVAT from SAT or VAT. "
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    ABSTRACT: The perivascular adipose tissue (PVAT) is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT.
    Vascular Health and Risk Management 03/2013; 9:105-16. DOI:10.2147/VHRM.S33760
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    • "SVF from eWAT or inter-scapular BAT from 8 week old mice were isolated as described (Fitzgibbons et al., 2011), and stained with blue stain (Invitrogen) at 4°C for 20 min. Cells were incubated with anti-mouse CD16/CD32 (BD Biosciences) for 15 min and then with respective FACS antibody for 2h at room temperature. "
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    ABSTRACT: Adipose tissue expansion involves the enlargement of existing adipocytes, the formation of new cells from committed preadipocytes, and the coordinated development of the tissue vascular network. Here we find that murine endothelial cells (ECs) of classic white and brown fat depots share ultrastructural characteristics with pericytes, which are pluripotent and can potentially give rise to preadipocytes. Lineage tracing experiments using the VE-cadherin promoter reveal localization of reporter genes in ECs and also in preadipocytes and adipocytes of white and brown fat depots. Furthermore, capillary sprouts from human adipose tissue, which have predominantly EC characteristics, are found to express Zfp423, a recently identified marker of preadipocyte determination. In response to PPARγ activation, endothelial characteristics of sprouting cells are progressively lost, and cells form structurally and biochemically defined adipocytes. Together these data support an endothelial origin of murine and human adipocytes, suggesting a model for how adipogenesis and angiogenesis are coordinated during adipose tissue expansion.
    Cell metabolism 02/2012; 15(2):222-9. DOI:10.1016/j.cmet.2012.01.008 · 17.57 Impact Factor
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