Adipokines nouvellement impliquées dans l'obésité humaine : régulation et rôle dans le développement du syndrome métabolique
(2009)
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- Authors
- Supervisors
- Brichard, Sonia
- Abstract
- (en) Accumulation of visceral rather than subcutaneous fat is an established risk factor for the pathogenesis of the metabolic syndrome. Adipose tissue secretes a variety of bioactive peptides, collectively referred to “adipokines” which may be involved in these obesity-related disorders. However, comparison of secretome analysis between visceral adipose tissue of obese individuals and that of lean ones has not been performed. In this context, we carried out adipokine secretion profile of human visceral adipose tissue and examined adipokines differentially secreted between lean and obese subjects. We identified 6 adipokines as oversecreted by human visceral adipose tissue in obesity: 3 chemokines [Growth-Related Oncogen factor (GRO), Regulated upon Activation Normal T cells Expressed and Secreted (RANTES), Macrophage Inflammatory Protein-1ß (MIP-1β)], 1 tissue inhibitor of metalloproteinases (TIMP-1), 1 megakaryocytic growth factor (Thrombopoietin, TPO) and 1 interleukin (IL-7). Both adipocytes and stromal-vascular cells contributed to their altered secretion. Enhanced expression of these adipokines in adipocytes did correlate with several features of the metabolic syndrome. In addition, circulating GRO-α, TPO and TIMP-1 levels were increased in obesity, as already demonstrated for RANTES. As these adipokines are involved in cardiovascular disease and/or type 2 diabetes, our results may provide new insight into the pathogenesis of the metabolic syndrome. Eventually, we investigated the molecular mechanisms leading to this adipokine overproduction. We showed that TNF-α was, over all the numerous factors secreted by stromal-vascular cells, a crucial determinant of adipokine dysregulation in visceral adipocytes of obese subjects. This cytokine appears to be a potent and proximal molecule in the hierarchy of cytokines’ and chemokines’ networks of adipose tissue. TNF-α, which is oversecreted by stromal-vascular cells in obesity, acts on enlarged adipocytes, which are hyper-responsive to this triggering signal. This adipocyte hyper-responsiveness results in adipokine overproduction through TNFR1 and hyper-activation of NF-��B. This amplified paracrine cross-talk between adipocytes and SVC in human obesity ultimately leads to worsening of the inflammatory state and the metabolic syndrome. Targeting altered TNF-α production, events of the TNF-α signalling cascade or the adipocyte hyper-responsiveness may have therapeutic potential for the management of the metabolic syndrome.
- Affiliations
Citations
Maury, E. (2009). Adipokines nouvellement impliquées dans l’obésité humaine : régulation et rôle dans le développement du syndrome métabolique. https://hdl.handle.net/2078.5/131093