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

Nat Genet. 2005 Oct;37(10):1072-81. doi: 10.1038/ng1642. Epub 2005 Sep 18.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Disease Models, Animal
  • Gene Deletion
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Insulin / blood
  • Leptin / blood
  • Lipid Metabolism / genetics*
  • Lipids / analysis
  • Liver / metabolism
  • Lymph / metabolism
  • Lymphatic Abnormalities / complications
  • Lymphatic Abnormalities / genetics*
  • Lymphatic Vessels / abnormalities
  • Lymphatic Vessels / physiopathology
  • Mice
  • Mice, Knockout
  • Obesity / complications
  • Obesity / genetics*
  • Tumor Suppressor Proteins

Substances

  • Homeodomain Proteins
  • Insulin
  • Leptin
  • Lipids
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein