نبذة مختصرة : Obesity comprises great risks for human health, contributing to the development of other diseases such as metabolic syndrome, type 2 diabetes and cardiovascular disease. Previously, obese patients were found to have elevated serum levels of VEGF-C, which correlated with worsening of lipid parameters. We recently identified that neutralization of VEGF-C and -D in the subcutaneous adipose tissue during the development of obesity improves metabolic parameters and insulin sensitivity in mice. To test the hypothesis that VEGF-C plays a role in the promotion of the metabolic disease, we used K14-VEGF-C mice that overexpress human VEGF-C under control of the keratin-14 promoter in the skin and monitored metabolic parameters over time. K14-VEGF-C mice had high levels of VEGF-C in the subcutaneous adipose tissue and gained more weight than wildtype littermates, became insulin resistant and had increased ectopic lipid accumulation at 20 weeks of age on regular mouse chow. The metabolic differences persisted under high-fat diet induced obesity. These results indicate that elevated VEGF-C levels contribute to metabolic deterioration and the development of insulin resistance, and that blockade of VEGF-C in obesity represents a suitable approach to alleviate the development of insulin resistance. ; Peer reviewed
Relation: We thank Jeannette Scholl, Arian Kazimi, Steven Proulx, Eric Haertel, Susanna Poghosyan, Samia Bachmann and Gitalee Sarker for technical assistance and help with experiments and the Scientific Center for Optical and Electron Microscopy ScopeM of the ETH Zurich for providing imaging facilities. Indirect calorimetry studies were performed at Vanderbilt Mouse Metabolic Phenotyping Center (DK059637). This work was supported by Swiss National Science Foundation grant 310030B_147087, European Research Council grant LYVICAM, Oncosuisse, Krebsliga Zurich (all to M.D.) and Leducq Foundation Transatlantic Network of Excellence grant Lymph Vessels in Obesity and Cardiovascular Disease (11CVD03, to M.D. and K.A.). M.H. was supported by the Sigrid Juselius Foundation and the Instrumentarium Foundation. Studies in the laboratory of K.A. were also supported by the Academy of Finland and the European Research Council (ERC-2010-AdG-268804).; Karaman , S , Hollmen , M , Yoon , S-Y , Alkan , H F , Alitalo , K , Wolfrum , C & Detmar , M 2016 , ' Transgenic overexpression of VEGF-C induces weight gain and insulin resistance in mice ' , Scientific Reports , vol. 6 , 31566 . https://doi.org/10.1038/srep31566; ORCID: /0000-0002-0719-1773/work/54151484; http://hdl.handle.net/10138/166449; 0d4f674d-2efe-4ae5-95ac-89903b6f0991; 84982182472; 000381190700001
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