Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity

NL Harvey, RS Srinivasan, ME Dillard, NC Johnson… - Nature …, 2005 - nature.com
NL Harvey, RS Srinivasan, ME Dillard, NC Johnson, MH Witte, K Boyd, MW Sleeman…
Nature genetics, 2005nature.com
Multiple organs cooperate to regulate appetite, metabolism, and glucose and fatty acid
homeostasis. Here, we identified and characterized lymphatic vasculature dysfunction as a
cause of adult-onset obesity. We found that functional inactivation of a single allele of the
homeobox gene Prox1 led to adult-onset obesity due to abnormal lymph leakage from
mispatterned and ruptured lymphatic vessels. Prox1 heterozygous mice are a new model for
adult-onset obesity and lymphatic vascular disease.
Abstract
Multiple organs cooperate to regulate appetite, metabolism, and glucose and fatty acid homeostasis. Here, we identified and characterized lymphatic vasculature dysfunction as a cause of adult-onset obesity. We found that functional inactivation of a single allele of the homeobox gene Prox1 led to adult-onset obesity due to abnormal lymph leakage from mispatterned and ruptured lymphatic vessels. Prox1 heterozygous mice are a new model for adult-onset obesity and lymphatic vascular disease.
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