Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation
01 Oct 2011-American Journal of Physiology-heart and Circulatory Physiology (American Physiological Society)-Vol. 301, Iss: 4
TL;DR: In this article, perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and metabolic syndrome.
Abstract: 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...
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TL;DR: The mechanisms by which dysfunctional adipose tissue simultaneously promote T2DM and CVD, focusing on adipose tissues depot-specific adipokines, inflammatory profiles, and metabolism, will be the focus of this review.
Abstract: Adipose tissue plays essential roles in maintaining lipid and glucose homeostasis. To date several types of adipose tissue have been identified, namely white, brown, and beige, that reside in various specific anatomical locations throughout the body. The cellular composition, secretome, and location of these adipose depots define their function in health and metabolic disease. In obesity, adipose tissue becomes dysfunctional, promoting a pro-inflammatory, hyperlipidemic and insulin resistant environment that contributes to type 2 diabetes mellitus (T2DM). Concurrently, similar features that result from adipose tissue dysfunction also promote cardiovascular disease (CVD) by mechanisms that can be augmented by T2DM. The mechanisms by which dysfunctional adipose tissue simultaneously promote T2DM and CVD, focusing on adipose tissue depot-specific adipokines, inflammatory profiles, and metabolism, will be the focus of this review. The impact that various T2DM and CVD treatment strategies have on adipose tissue function and body weight also will be discussed.
476 citations
Cites background from "Similarity of mouse perivascular an..."
...Healthy PVAT is thought to be a largely anti-inflammatory tissue (330), with characteristics akin to BAT in the areas surrounding the thoracic aorta in particular (331)....
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...In one study, BAT isolated from mice made obese by 13 weeks of high fat diet feeding displayed lower mRNA expression of inflammatory genes, lower immunostaining for macrophagemarkers F4/80 and CD68, and lower macrophage content by FACS analysis (331)....
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TL;DR: F Fate-mapping analyses have identified progenitor populations that give rise to brown and beige fat cells, and have revealed unanticipated cell-lineage relationships between vascular smooth muscle cells and bege adipocytes, and between skeletal Muscle cells and brown fat.
Abstract: Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight. Brown adipocytes develop in discrete and relatively homogenous depots of brown adipose tissue, whereas beige adipocytes are induced to develop in white adipose tissue in response to certain stimuli - notably, exposure to cold. Fate-mapping analyses have identified progenitor populations that give rise to brown and beige fat cells, and have revealed unanticipated cell-lineage relationships between vascular smooth muscle cells and beige adipocytes, and between skeletal muscle cells and brown fat. In addition, non-adipocyte cells in adipose tissue, including neurons, blood vessel-associated cells and immune cells, have crucial roles in regulating the differentiation and function of brown and beige fat.
465 citations
TL;DR: This review focuses on the microenvironment of adipose tissue and how it influences cardiovascular disorders, including atherosclerosis and ischemic heart diseases, through the systemic actions of adipokines.
Abstract: Obesity is causally linked with the development of cardiovascular disorders. Accumulating evidence indicates that cardiovascular disease is the collateral damage of obesity-driven adipose tissue dysfunction that promotes a chronic inflammatory state within the organism. Adipose tissues secrete bioactive substances, referred to as adipokines, which largely function as modulators of inflammation. The microenvironment of adipose tissue will affect the adipokine secretome, having actions on remote tissues. Obesity typically leads to the upregulation of proinflammatory adipokines and the downregulation of anti-inflammatory adipokines, thereby contributing to the pathogenesis of cardiovascular diseases. In this review, we focus on the microenvironment of adipose tissue and how it influences cardiovascular disorders, including atherosclerosis and ischemic heart diseases, through the systemic actions of adipokines.
418 citations
TL;DR: The need to better understand the mechanisms linking visceral adiposity with liver fat accumulation, the mechanisms by which ectopic fat accumulation cause insulin resistance, and the size of adipose tissue depots is determined is underscored.
Abstract: Purpose of review
The association between obesity and insulin resistance is an area of much interest and enormous public health impact, with hundreds of articles being published in the last year focused on the possible mechanisms that underlie this association. The purpose to this review is to highlight some of the key recent literature with emphasis on emerging concepts.
411 citations
TL;DR: It is found that murine endothelial cells of classic white and brown fat depots share ultrastructural characteristics with pericytes, which are pluripotent and can potentially give rise to preadipocytes, suggesting an endothelial origin of murine and human adipocytes.
320 citations
Additional excerpts
...SVF from eWAT and interscapular 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....
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...Fluorescence-Activated Cell Sorting SVF from eWAT and interscapular 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....
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References
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TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.
139,407 citations
Harvard University1, Brigham and Women's Hospital2, University of Wisconsin-Madison3, University of California, Berkeley4, Technical University of Denmark5, Icahn School of Medicine at Mount Sinai6, Vienna University of Technology7, University of Erlangen-Nuremberg8, German Cancer Research Center9, University of Milan10, Johns Hopkins University11, University of Washington12, Scripps Research Institute13, Walter and Eliza Hall Institute of Medical Research14, University of Iowa15
TL;DR: Details of the aims and methods of Bioconductor, the collaborative creation of extensible software for computational biology and bioinformatics, and current challenges are described.
Abstract: The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples.
12,142 citations
"Similarity of mouse perivascular an..." refers methods in this paper
...Bioconductor project (12) using the statistical computing language R...
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TL;DR: The Gene Expression Omnibus (GEO) project was initiated in response to the growing demand for a public repository for high-throughput gene expression data and provides a flexible and open design that facilitates submission, storage and retrieval of heterogeneous data sets from high-power gene expression and genomic hybridization experiments.
Abstract: The Gene Expression Omnibus (GEO) project was initiated in response to the growing demand for a public repository for high-throughput gene expression data. GEO provides a flexible and open design that facilitates submission, storage and retrieval of heterogeneous data sets from high-throughput gene expression and genomic hybridization experiments. GEO is not intended to replace in house gene expression databases that benefit from coherent data sets, and which are constructed to facilitate a particular analytic method, but rather complement these by acting as a tertiary, central data distribution hub. The three central data entities of GEO are platforms, samples and series, and were designed with gene expression and genomic hybridization experiments in mind. A platform is, essentially, a list of probes that define what set of molecules may be detected. A sample describes the set of molecules that are being probed and references a single platform used to generate its molecular abundance data. A series organizes samples into the meaningful data sets which make up an experiment. The GEO repository is publicly accessible through the World Wide Web at http://www.ncbi.nlm.nih.gov/geo.
10,968 citations
"Similarity of mouse perivascular an..." refers background in this paper
...The data discussed in this publication have been deposited in NCBI’s Gene Expression Omnibus (9) and are accessible through GEO Series Accession No....
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...Gene Expression Omnibus (9) and are accessible through GEO Series...
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TL;DR: Three methods of performing normalization at the probe intensity level are presented: a one number scaling based algorithm and a method that uses a non-linear normalizing relation by comparing the variability and bias of an expression measure and the simplest and quickest complete data method is found to perform favorably.
Abstract: Motivation: When running experiments that involve multiple high density oligonucleotide arrays, it is important to remove sources of variation between arrays of non-biological origin. Normalization is a process for reducing this variation. It is common to see non-linear relations between arrays and the standard normalization provided by Affymetrix does not perform well in these situations. Results: We present three methods of performing normalization at the probe intensity level. These methods are called complete data methods because they make use of data from all arrays in an experiment to form the normalizing relation. These algorithms are compared to two methods that make use of a baseline array: a one number scaling based algorithm and a method that uses a non-linear normalizing relation by comparing the variability and bias of an expression measure. Two publicly available datasets are used to carry out the comparisons. The simplest and quickest complete data method is found to perform favorably. Availabilty: Software implementing all three of the complete data normalization methods is available as part of the R package Affy, which is a part of the Bioconductor project http://www.bioconductor.org. Contact: bolstad@stat.berkeley.edu Supplementary information: Additional figures may be found at http://www.stat.berkeley.edu/∼bolstad/normalize/ index.html
8,324 citations
"Similarity of mouse perivascular an..." refers methods in this paper
...Second-strand cDNA was then labeled with the Affymetrix WT terminal labeling kit, and samples were hybridized to Affymetrix Mouse Gene 1.0 ST arrays (Affymetrix, Santa Clara, CA)....
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...mented as a function of the R package Affy (2), which is part of the...
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...The algorithm was implemented as a function of the R package Affy (2), which is part of the Bioconductor project (12) using the statistical computing language R (R Foundation for Statistical Computing, Vienna, Austria)....
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...Total RNA was hybridized to Affymetrix Mouse Gene 1.0 ST chips, each of which contains probes targeting 28,853 genes....
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TL;DR: It is proposed that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue, and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance.
Abstract: Insulin resistance arises from the inability of insulin to act normally in regulating nutrient metabolism in peripheral tissues Increasing evidence from human population studies and animal research has established correlative as well as causative links between chronic inflammation and insulin resistance However, the underlying molecular pathways are largely unknown In this report, we show that many inflammation and macrophage-specific genes are dramatically upregulated in white adipose tissue (WAT) in mouse models of genetic and high-fat diet-induced obesity (DIO) The upregulation is progressively increased in WAT of mice with DIO and precedes a dramatic increase in circulating-insulin level Upon treatment with rosiglitazone, an insulin-sensitizing drug, these macrophage-originated genes are downregulated Histologically, there is evidence of significant infiltration of macrophages, but not neutrophils and lymphocytes, into WAT of obese mice, with signs of adipocyte lipolysis and formation of multinucleate giant cells These data suggest that macrophages in WAT play an active role in morbid obesity and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance We propose that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue
6,165 citations
"Similarity of mouse perivascular an..." refers background in this paper
...CD68 and F4/80 markers define total macrophage populations in adipose tissue but do not differentiate between cells at various levels of activation (43, 45, 46)....
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...(46) reported that genetic and dietinduced obesity resulted in chronic inflammation in WAT but not BAT....
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