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

• Published in: Nature genetics Vol. 37; no. 10; pp. 1072 - 1081
• Main Authors: Oliver, Guillermo, Harvey, Natasha L, Srinivasan, R Sathish, Dillard, Miriam E, Johnson, Nicole C, Witte, Marlys H, Boyd, Kelli, Sleeman, Mark W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-10-2005
• Subjects: Alleles; Animals; Biological and medical sciences; Blood circulation disorders; Complications and side effects; Diagnosis; Disease Models, Animal; Fatty acids; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene expression; Genetic aspects; Genetics of eukaryotes. Biological and molecular evolution; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Inactivation; 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; Medical sciences; Metabolic diseases; Mice; Mice, Knockout; Obesity; Obesity - complications; Obesity - genetics; Physiological aspects; Risk factors; Tumor Suppressor Proteins; Vascular diseases; United States; Human; Obesity; Adult; Nutritional status; Nutrition disorder
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1642

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.