Carboxypeptidase E and thrombospondin-1 are differently expressed in subcutaneous and visceral fat of obese subjects

Ramis, Joana Maria; Hal, Nicole L.W. Franssen-van; Kramer, Evelien; Lladó, Isabel; Bouillaud, Frédéric; Palou, Andreu; Keijer, Jaap

doi:10.1007/pl00012518

Cited by 57 publications

(46 citation statements)

References 37 publications

(38 reference statements)

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“…However, not all adipose depots secrete the same relative proportion of adipokines, and a number of differences in adipokine expression have been described between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (4). One such protein of interest is thrombospondin (TSP)1, which in one brief study was preferentially expressed in VAT compared with SAT (5). Increased TSP1 expression has been reported in adipose tissue of obese rodents (6,7); however, the cell of origin in adipose has not been determined.…”

Section: -439 2008mentioning

confidence: 99%

Thrombospondin-1 Is an Adipokine Associated With Obesity, Adipose Inflammation, and Insulin Resistance

et al. 2008

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OBJECTIVE-We examined the relationship between the expression of thrombospondin (TSP)1, an antiangiogenic factor and regulator of transforming growth factor-␤ activity, obesity, adipose inflammation, and insulin resistance.RESEARCH DESIGN AND METHODS-TSP1 gene expression was quantified in subcutaneous adipose tissue (SAT) of 86 nondiabetic subjects covering a wide range of BMI and insulin sensitivity, from visceral adipose (VAT) and SAT from 14 surgical patients and from 38 subjects with impaired glucose tolerance randomized to receive either pioglitazone or metformin for 10 weeks. An adipocyte culture system was also used to assess the effects of pioglitazone and coculture with macrophages on TSP1 gene expression. RESULTS-TSP1mRNA was significantly associated with obesity (BMI) and insulin resistance (low insulin sensitivity index). Relatively strong positive associations were seen with markers of inflammation, including CD68, macrophage chemoattractant protein-1, and plasminogen activator inhibitor (PAI)-1 mRNA (r Ն 0.46, P ϭ 0.001 for each), that remained significant after controlling for BMI and S i . However, TSP1 mRNA was preferentially expressed in adipocyte fraction, whereas inflammatory markers predominated in stromal vascular fraction. Coculture of adipocytes and macrophages augmented TSP1 gene expression and secretion from both cell types. Pioglitazone (not metformin) treatment resulted in a 54% decrease (P Ͻ 0.04) in adipose TSP gene expression, as did in vitro pioglitazone treatment of adipocytes.CONCLUSIONS-TSP1 is a true adipokine that is highly expressed in obese, insulin-resistant subjects; is highly correlated with adipose inflammation; and is decreased by pioglitazone. TSP1 is an important link between adipocytes and macrophagedriven adipose tissue inflammation and may mediate the elevation of PAI-1 that promotes a prothrombotic state. Diabetes 57: 432-439, 2008

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Section: -439 2008mentioning

confidence: 99%

Thrombospondin-1 Is an Adipokine Associated With Obesity, Adipose Inflammation, and Insulin Resistance

et al. 2008

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“…Recently, this protein has been included among the group of adipokines, since its expression is increased in WAT of obese and insulin-resistant subjects, presenting positive correlations with the level of adiposity [35,41]. Furthermore, it has been reported as an important factor in the adipocyte-and macrophage-driven inflammation in the adipose tissue, and that could mediate the elevation of PAI-1, promoting a prothrombotic state [41].…”

Section: Introductionmentioning

confidence: 99%

“…Also, TSP-1 has been described as a major regulator of the transforming growth factor (TGF)-β activity [11,31], which, together with the increased 3 PAI-1 levels, are correlated with different features of obesity, insulin-resistance, and metabolic syndrome [1,29,37]. Finally, it has been described higher TSP-1 gene expression in visceral respect to subcutaneous adipose tissue in obese subjects [35].…”

Section: Introductionmentioning

confidence: 99%

Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats

et al. 2011

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Thrombospondin 1 (TSP-1), an anti-angiogenic factor and TGF-β activity regulator, has been recently recognized as an adipokine that correlates with obesity, inflammation and insulin-resistance processes. In the present study, epididymal adipocytes of rats that were fed a chow (C) or a high fat diet (HFD) for 50 days, were isolated and incubated (24-72 h) in low (LG; 5.6 mM) or high (HG; 25 mM) glucose, in presence or absence of 1.6 nM insulin. Rats fed the HF diet showed an established obesity state. Serum TSP-1 levels and TSP-1 mRNA basal expression of adipocytes from HFD rats were higher than those from controls. Adipocytes from HFD animals presented an insulin-resistance state, as suggested by the lower insulin-stimulated glucose uptake as compared to controls. TSP-1 expression in culture was higher in adipocytes from obese animals at 24 h, but when the adipocytes were treated with HG, these expression levels dropped dramatically. Later at 72 h, TSP-1 expression was lower in adipocytes from HFD rats, and no effects of the other treatments were observed. Surprisingly, the secretion levels of this protein at 72 h were increased significantly by the HG treatment in both types of adipocytes, although they were even higher in adipocytes from obese animals. Finally, cell viability was significantly reduced by HG treatment in both types of adipocytes. In summary, TSP-1 expression/secretion was modulated in an in vitro model of insulinresistant adipocytes. The difference between expression and secretion patterns suggests a post-transcriptional regulation. The present study confirms that TPS-1 is closely associated with obesity-related mechanisms.

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“…In studies primarily performed on adipose tissue of extreme obese individuals using several different techniques, including microarray technology [18,46,57], representational display analysis [40] and quantitative polymerase chain reaction (PCR) [14,24,43], Leptin [14,24,43,50,57], calcyclin, adipsin [40,63] and perilipin [2] were shown to be more highly expressed in the subcutaneous depot, while thrombospondin and carboxypeptidase E [46] were found to be more highly expressed in the omental depot. This confirmed the existence of functional differences between different depots.…”

Section: Introductionmentioning

confidence: 99%

Intra- and interindividual variation in gene expression in human adipose tissue

Beek¹,

Bakker

Kruyt

et al. 2006

Pflugers Arch - Eur J Physiol

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Carboxypeptidase E and thrombospondin-1 are differently expressed in subcutaneous and visceral fat of obese subjects

Cited by 57 publications

References 37 publications

Thrombospondin-1 Is an Adipokine Associated With Obesity, Adipose Inflammation, and Insulin Resistance

Thrombospondin-1 Is an Adipokine Associated With Obesity, Adipose Inflammation, and Insulin Resistance

Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats

Intra- and interindividual variation in gene expression in human adipose tissue

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