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Adipose tissue dysfunction in obesity, diabetes, and vascular diseases by Gideon R. Hajer, Timon W. van Haeften, and Frank L.J. Visseren EHJ Volume ():

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Presentation on theme: "Adipose tissue dysfunction in obesity, diabetes, and vascular diseases by Gideon R. Hajer, Timon W. van Haeften, and Frank L.J. Visseren EHJ Volume ():"— Presentation transcript:

1 Adipose tissue dysfunction in obesity, diabetes, and vascular diseases by Gideon R. Hajer, Timon W. van Haeften, and Frank L.J. Visseren EHJ Volume (): September 5, 2008 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

2 Leptin and adiponectin: leptin acts primarily via the melanocortin system (arcuate nucleus) in the hypothalamus15 where it inhibits 5'AMP-activated protein kinase,20 resulting in decreased hunger and stimulated energy expenditure8,17 and, to a lesser extent, in enhancing growth (growth hormone) and reproduction by stimulating gonadotrophin releasing hormone in both men and women.20 In peripheral tissues, leptin increases lipid oxidation (liver) and lipolysis (skeletal muscle and adipocytes). Gideon R. Hajer et al. Eur Heart J 2008;eurheartj.ehn387 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

3 Adipocyte–macrophage interaction leading to dysfunction: as adipocytes enlarge, increased levels of adipocyte-derived free fatty acids (FFAs) are released which can stimulate the already present macrophages to produce tumour necrosis factor-α (TNF-α). Gideon R. Hajer et al. Eur Heart J 2008;eurheartj.ehn387 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

4 Adipocyte dysfunction leads to insulin resistance: tumour necrosis factor-α (TNF-α), interleukin- 6 (IL-6), and free fatty acids (FFAs) induce serine phosphorylation of insulin receptor substrate-1 and insulin receptor substrate-2, which reduces the capacity of insulin receptor substrate proteins to be phosphorylated by the insulin receptor in vitro and may even inhibit insulin receptor autophosphorylation (tyrosine kinase) activity, thereby further attenuating the insulin signalling cascade. Gideon R. Hajer et al. Eur Heart J 2008;eurheartj.ehn387 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

5 Adipocyte dysfunction leads to type 2 diabetes: chronically elevated free fatty acid (FFA) levels inhibit insulin secretion.73 In vitro, long-chain fatty-acyl-CoA and FFA can open β-cell potassium channels which diminish insulin secretion. Gideon R. Hajer et al. Eur Heart J 2008;eurheartj.ehn387 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

6 Adipocyte dysfunction leads to atherosclerosis (trident mark: ICAM-1, paragraph mark: vascular cell adhesion molecule-1, beaker symbol: scavenger receptor class A-1: platelets). Gideon R. Hajer et al. Eur Heart J 2008;eurheartj.ehn387 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

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