title: Elastin Insufficiency Predisposes Mice to Impaired Glucose Metabolism.
abstract: Williams-Beuren syndrome is the consequence of a large contiguous-gene deletion on the seventh human chromosome that includes the elastin gene. Elastin is an extracellular matrix protein responsible for the cardiovascular abnormalities associated with Williams's syndrome, including hypertension and aortic stenosis. A high percentage of individuals with Williams's syndrome also have impaired glucose tolerance, independent of traditional risk factors for diabetes. Here, we show that murine adipose tissue does assemble elastic fibers; however, isolated elastin insufficiency (Eln+/-) in mice does not independently influence glucose metabolism or tissue lipid accumulation. Similarly, isolated ApoE deficiency (ApoE-/-), a model of hyperlipidemia and atherosclerosis, does not impair insulin sensitivity. However,Eln+/-;ApoE-/-double mutant mice exhibit notable hyperglycemia, adipocyte hypertrophy, inflammation of adipose tissue, and ectopic lipid accumulation in liver tissue. Further,Eln+/-;ApoE-/-mutants have significant impairment of insulin sensitivity by insulin tolerance testing, independent of body weight or diet, suggesting that elastin insufficiency predisposes to metabolic disease in susceptible individuals.
authors.affiliation: Department of Cell Biology & Physiology, Washington University in St. Louis, MO, USA.
authors.forename: Antea J
authors.initials: AJ
authors.lastname: DeMarsilis
authors.affiliation: Department of Cell Biology & Physiology, Washington University in St. Louis, MO, USA.
authors.forename: Tezin A
authors.initials: TA
authors.lastname: Walji
authors.affiliation: Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, MO, USA.
authors.forename: Justine A
authors.initials: JA
authors.lastname: Maedeker
authors.affiliation: Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, MO, USA.
authors.forename: Kellie V
authors.initials: KV
authors.lastname: Stoka
authors.affiliation: Department of Pediatrics,, Washington University in St. Louis, MO, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Kozel
authors.affiliation: Department of Cell Biology & Physiology, Washington University in St. Louis, MO, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mecham
authors.affiliation: Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, MO, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Wagenseil
authors.affiliation: Department of Cell Biology & Physiology, Washington University in St. Louis, MO, USA.
authors.forename: Clarissa S
authors.initials: CS
authors.lastname: Craft
keywords: Adipose tissue; Apolipoprotein E; Cardiovascular disease; Diabetes; Elastic fiber; Elastin; Williams syndrome