Linked Life Data

18381283

Source:http://linkedlifedata.com/resource/pubmed/id/18381283

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2008-6-9
pubmed:abstractText
Obesity, diabetes, insulin resistance, and hyperinsulinemia are frequently associated with a cluster of closely related lipid abnormalities such as low plasma levels of high density lipoprotein (HDL) and elevated levels of triglyceride, both known to increase the risk of developing atherosclerotic disease. The molecular mechanisms linking obesity, insulin resistance, and hyperinsulinemia to low HDL levels are incompletely understood. Here we demonstrate that insulin, through a Foxa2-mediated mechanism, inhibited the expression of apolipoprotein M (apoM), an important determinant of plasma pre-beta-HDL and alpha-HDL concentrations. Obese mice had decreased apoM expression and plasma pre-beta-HDL levels due to inactivation of Foxa2 in hyperinsulinemic states. Nuclear reexpression of Foxa2 with a phosphorylation-deficient mutant Foxa2T156A (Ad-T156A) activated apoM expression and increased plasma pre-beta-HDL and alpha-HDL levels. In contrast, haploinsufficient Foxa2(+/-) mice exhibited decreased hepatic apoM expression and plasma pre-beta-HDL and HDL levels. The increase in plasma HDL levels and pre-beta-HDL formation by Foxa2 was mediated exclusively by apoM, as constitutive active expression of Foxa2 in apoM(-/-) mice had no effect on plasma HDL levels. Our results identify a fundamental mechanism by which insulin regulates plasma HDL levels in physiological and insulin-resistant states and thus have important implications for novel therapeutic approaches to prevent atherosclerosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16940-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Foxa2 activity increases plasma high density lipoprotein levels by regulating apolipoprotein M.
pubmed:affiliation
Institute of Molecular Systems Biology, Swiss Federal Institute of Technology, Eidgenössische Technische Hochschule Zürich, 8093 Zürich, Switzerland.
pubmed:publicationType
Journal Article