title: Transgenic overexpression of VEGF-C induces weight gain and insulin resistance in mice.
abstract: 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.
authors: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors: Sinem
authors: S
authors: Karaman
authors: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors: Maija
authors: M
authors: Hollmén
authors: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors: Sun-Young
authors: SY
authors: Yoon
authors: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors: H Furkan
authors: HF
authors: Alkan
authors: Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Finland.
authors: Kari
authors: K
authors: Alitalo
authors: Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology, ETH Zurich, 8603 Schwerzenbach, Switzerland.
authors: Christian
authors: C
authors: Wolfrum
authors: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland.
authors: Michael
authors: M
authors: Detmar
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance; D053547:Keratin-14 / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D050151:Subcutaneous Fat / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D053547:Keratin-14; C507446:Krt14 protein, mouse; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C