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New mechanisms of angiogenesis modulators in switching between white and brown adipose tissues

Final Report Summary - ANGIOFAT (New mechanisms of angiogenesis modulators in switching between white and brown adipose tissues)

During this 5-year ERC supported period, we have made significant achievements in understanding the role of vasculatures in modulating adipose tissue functions. We have carefully dissected each of the vascular cellular compartments and signaling pathways that mediate the crosstalk between adipocytes and vascular cells. We have found that under different physiological and pathological conditions, vascular cells might employ different signaling systems to modulate adipocyte functions. For example, during cold exposure browning of white adipocytes produce high levels of VEGF that acts on endothelial cells. The VEGF-stimulated endothelial cells produce other cytokines to modulate adipocyte differentiation and functions. In this reciprocal interactive scenario, the vascular cell compartment could play a dominant role in determining the adipocyte functions. In another published study (Cell Metab. 2013 Jul 2;18(1):118-29), we show that cold-induced angiogenesis-dependent lipolysis augments atherosclerotic plaque growth, leading to increases of cardiovascular risks. Moreover, we have also discovered a novel mechanism by which adipose vasculatures and VEGF differentially modulate insulin sensitivity in various age groups. This discovery suggests targeting the adipose vasculature provide a novel approach for treatment T2-diabetes (Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):14906-11.). Meanwhile, we have developed several novel methods to study the structures and functions of adipose vasculatures (Nat Protoc. 2010 May;5(5):912-20; Nat Protoc. 2012 Mar 1;7(3):606-15.). These methods are now routinely used by other laboratories. We ensured our international leading position in proposing new hypotheses and ideas of adipose angiogenesis by publishing our concepts in leading international journals including: Nat Rev Drug Discov. 2010 Feb;9(2):107-15; Cell Metab. 2013 Oct 1;18(4):478-89..