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Publication
Transgenic overexpression of VEGF-C induces weight gain and insulin resistance
in mice.
Authors Karaman S, Hollmén M, Yoon SY, Alkan HF, Alitalo K, Wolfrum C, Detmar M
Submitted By Michael Detmar on 8/17/2016
Status Published
Journal Scientific reports
Year 2016
Date Published
Volume : Pages 6 : 31566
PubMed Reference 27511834
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.




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