Adipose Tissue Collagen VI in Obesity

Pasarica, Magdalena; Gowronska-Kozak, Barbara; Burk, David H.; Remedios, Isabel; Hymel, David; Gimble, Jeff; Ravussin, Éric; Bray, George A.; Smith, Steven R.

doi:10.1210/jc.2009-0947

Cited by 286 publications

(272 citation statements)

References 22 publications

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“…The expression of procollagen α3(VI) is regulated by PPARγ and our findings are in alignment with this. In fact, procollagen α3(VI) mRNA is suppressed by PPARγ, as demonstrated by an increase in procollagen α3(VI) mRNA expression in adipocyte cultures treated with siRNA against PPARγ [9] and by a decrease in its transcripts in subcutaneous adipose tissue of individuals with type 2 diabetes treated with the PPARγ agonist pioglitazone, especially in patients with high baseline tissue levels of procollagen α3(VI) mRNA [12]. These data may in part explain the change in correlation, from baseline to the end of glitazone treatment, between endotrophin serum levels and HbA 1c or HOMA-IR, and in particular the lack of a correlation between endotrophin and the metabolic variables.…”

Section: Discussionmentioning

confidence: 99%

“…Endotrophin is predominantly produced by adipose tissue and induces upregulation of TGF-β, adipose tissue fibrosis, angiogenesis and inflammation [8]. In animal models, it has also been shown to unfavourably modulate several metabolic functions, such as insulin sensitivity, food intake, energy balance [8][9][10] and adipose tissue inflammation [11,12]. These findings suggest that levels of endotrophin in the blood may be useful for classifying and/or monitoring patients with metabolic dysfunction, especially those with type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

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Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes

et al. 2016

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Aims/hypothesis The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of procollagen type VI (also called Pro-C6), is involved in both adipose tissue matrix remodelling and metabolic control. We established a serum assay for endotrophin to assess if this novel adipokine could identify type 2 diabetic patients who respond optimally to PPARγ agonists, improving the risk-to-benefit ratio. Methods The BALLET trial (NCT00515632) compared the glucose-lowering effects and safety of the partial PPARγ agonist balaglitazone with those of pioglitazone in individuals with type 2 diabetes on stable insulin therapy. The per protocol population (n = 297) was stratified into tertiles based on baseline endotrophin levels. Participants were followed-up after 26 weeks, after which correlational analysis was carried out between endotrophin levels and measures of glucose control. This is a secondary post hoc analysis. Results Endotrophin was significantly associated with therapeutic response to balaglitazone and pioglitazone. At week 26, only individuals in the upper two tertiles showed significant reductions in HbA 1c and fasting serum glucose compared with baseline. The OR for a 1% and a 0.5% reduction in HbA 1c for individuals in the upper two tertiles were 3.83 (95% CI 1.62, 9.04) p < 0.01, and 3.85 (95% CI 1.94, 7.61) p < 0.001, respectively. Endotrophin levels correlated with adipose tissue mass, insulin resistance and fatty liver index. Notably, PPARγ-associated adverse effects, such as moderate-to-severe lower extremity oedema, only occurred in the lower tertile. Conclusions/interpretation Elevated endotrophin serum levels predict response to two insulin sensitisers and reduce the risk of associated adverse effects, thereby, identifying patients with type 2 diabetes who may profit from PPARγ agonist treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes

et al. 2016

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“…The ECM of adipose tissue, mainly represented by collagen VI (Scherer et al 1998), is dysfunctional in obesity and contributes to the development of the metabolic syndrome. Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis (Spencer et al 2010), and CO6A3 is higher in adipose tissue of obese women (Pasarica et al 2009). Increased collagen expression is also evident in the mesangium of diabetic rats (Abrass et al 1988).…”

Section: Structural Proteinsmentioning

confidence: 99%

2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue

Oliva

Barker

Rice

et al. 2013

Journal of Endocrinology

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Gestational diabetes mellitus (GDM) is a significant risk factor for the type 2 diabetes epidemic in many populations. Maternal adipose tissue plays a central role in the pathophysiology of GDM. Thus, the aim of this study was to determine the effect of GDM on the proteome of adipose tissue. Omental adipose tissue was obtained at the time of term Caesarean section from women with normal glucose tolerance (NGT) or GDM. 2D-difference gel electrophoresis (DIGE), followed by mass spectrometry, was used to identify protein spots (nZ6 patients per group). Western blotting was used for confirmation of six of the spot differences (nZ6 patients per group). We found 14 proteins that were differentially expressed between NGT and GDM adipose tissue (R1.4-fold, P!0.05). GDM was associated with an up-regulation of four proteins: collagen alpha-2(VI) chain (CO6A2 (COL6A2)), fibrinogen beta chain (FIBB (FGB)), lumican (LUM) and S100A9. On the other hand, a total of ten proteins were found to be down-regulated in adipose tissue from GDM women. These were alpha-1-antitrypsin (AIAT (SERPINA1)), annexin A5 (ANXA5), fatty acid-binding protein, adipocyte (FABP4), glutathione S-transferase P (GSTP (GSTP1)), heat-shock protein beta-1 (HSP27 (HSPB1)), lactate dehydrogenase B chain (LDHB), perilipin-1 (PLIN1), peroxiredoxin-6 (PRX6 (PRDX6)), selenium-binding protein 1 (SBP1) and vinculin (VINC (VCL)). In conclusion, proteomic analysis of omental fat reveals differential expression of several proteins in GDM patients and NGT pregnant women. This study revealed differences in expression of proteins that are involved in inflammation, lipid and glucose metabolism and oxidative stress and added further evidence to support the role of visceral adiposity in the pathogenesis of GDM.

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“…There is also evidence for reduced oxygen tension in adipose tissue of obese humans (Pasarica et al, 2009), although a recent report has challenged this view (Goossens et al, 2011). Hypoxia leads to important functional changes in adipocyte metabolism, including an increase in glucose utilisation Yin et al, 2009) and lactate production (Pérez de Heredia et al, 2010), indicative of enhanced glycolysis.…”

Section: Introductionmentioning

confidence: 99%

A microarray analysis of the hypoxia-induced modulation of gene expression in human adipocytes

Mazzatti

Lim

O’Hara

et al. 2012

Archives of Physiology and Biochemistry

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Adipose Tissue Collagen VI in Obesity

Abstract: These results are consistent with basic science data, suggesting that COL6A3 might contribute to adipose tissue inflammation.

Cited by 286 publications

References 22 publications

Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes

Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes

2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue

A microarray analysis of the hypoxia-induced modulation of gene expression in human adipocytes

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