Linked Life Data

21357939

Source:http://linkedlifedata.com/resource/pubmed/id/21357939

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-4-11
pubmed:abstractText
Low-grade inflammation in different tissues, including activation of the nuclear factor ?B pathway in liver, is involved in metabolic disorders such as type 2 diabetes and cardiovascular diseases (CVDs). In this study, we investigated the relation between chronic hepatocyte-specific overexpression of IkB kinase (IKK)-? and hypertriglyceridemia, an important risk factor for CVD, by evaluating whether activation of IKK-? only in the hepatocyte affects VLDL-triglyceride (TG) metabolism directly. Transgenic overexpression of constitutively active human IKK-? specifically in hepatocytes of hyperlipidemic APOE*3-Leiden mice clearly induced hypertriglyceridemia. Mechanistic in vivo studies revealed that the hypertriglyceridemia was caused by increased hepatic VLDL-TG production rather than a change in plasma VLDL-TG clearance. Studies in primary hepatocytes showed that IKK-? overexpression also enhances TG secretion in vitro, indicating a direct relation between IKK-? activation and TG production within the hepatocyte. Hepatic lipid analysis and hepatic gene expression analysis of pathways involved in lipid metabolism suggested that hepatocyte-specific IKK-? overexpression increases VLDL production not by increased steatosis or decreased FA oxidation, but most likely by carbohydrate-responsive element binding protein-mediated upregulation of Fas expression. These findings implicate that specific activation of inflammatory pathways exclusively within hepatocytes induces hypertriglyceridemia. Furthermore, we identify the hepatocytic IKK-? pathway as a possible target to treat hypertriglyceridemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
942-50
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Hepatocyte-specific IKK-? activation enhances VLDL-triglyceride production in APOE*3-Leiden mice.
pubmed:affiliation
Department of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands. J.A.van_Diepen@lumc.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't