Caractérisation d'IGFBP-2 comme biomarqueur intégrateur de la santé cardiométabolique
|Abstract:||Insulin-like growth factor binding protein (IGFBP)-2 is a circulating protein strongly associated with insulin resistance. IGFBP-2 modulates the metabolic actions of IGF-I and IGF-II by direct binding, but can also exert IGF-independent effects through extracellular matrix and integrin binding. In humans, lower IGFBP-2 levels are associated with a deleterious lipid profile, increased fat mass and decreased insulin sensitivity. Causal links between IGFBP-2 levels and surrogate markers of cardiometabolic risk and the potential of IGFBP-2 as a biomarker of metabolic alteration have been scarcely studied. The work presented herein shows in humans and mice that IGFBP-2 levels are independently associated with components of the metabolic syndrome. In men, low IGFBP-2 levels are associated with atherogenic dyslipidemia. A cut-off value for IGFBP-2 at 221.5 ng/mL allowed us to identify subjects with or without the metabolic syndrome. In addition to its association with insulin resistance and the components of the lipoprotein-lipid profile, low IGFBP-2 levels are linked to decreased cardiac function in aortic stenosis patients, as assessed by stroke volume index, a global marker of left ventricle function and remodeling. In men, high IGFBP-2 levels are associated with a more important volume of brown adipose tissue and an increased activity. These observations, as assessed by PET/CT, were also confirmed in mice overexpressing the human form of IGFBP-2. Our results show that IGFBP-2 levels are strongly associated to lipid metabolism, cardiac function and brown adipose tissue activity. The combined influence of different metabolic alterations on IGFBP-2 levels could make it an early and integrative biomarker. The work presented here highlights a potential mechanistic role for IGFBP-2 in the protection against certain metabolic alterations.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||24 April 2018|
|Collection:||Thèses et mémoires|
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