Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-7-28
pubmed:abstractText
Intestinal lipid dysregulation is a common feature of insulin-resistant states. The present study investigated alterations in gene expression of key proteins involved in the active absorption of dietary fat and cholesterol in response to development of insulin resistance. Studies were conducted in two diet-induced animal models of insulin resistance: fructose-fed hamster and high-fat-fed mouse. Changes in the mRNA abundance of lipid transporters, adenosine triphosphate cassette (ABC) G5, ABCG8, FA-CoA ligase fatty acid translocase P4, Niemann-Pick C1-Like1 (NPC1L1), fatty acid transport protein 4 (FATP4), and Scavenger Receptor Class B Type I (SR-BI), were assessed in intestinal fragments (duodenum, jejunum, and ileum) using quantitative real-time PCR. Of all the transporters evaluated, SR-B1 showed the most significant changes in both animal models examined. A marked stimulation of SR-B1 expression was observed in all intestinal segments examined in both insulin-resistant animal models. The link between SR-BI expression and intestinal lipoprotein production was then examined in the Caco-2 cell model. SR-B1 overexpression in Caco-2 cells increased apolipoprotein B (apoB) 100 and apoB48 secretion, whereas RNAi knock down of SR-B1 decreased secretion of both apoB100 and apoB48. We also observed changes in subcellular distribution of SR-B1 in response to exogenous lipid and insulin. Confocal microscopy revealed marked changes in SR-BI subcellular distribution in response to both exogenous lipids (oleate) and insulin. In summary, marked stimulation of intestinal SR-BI occurs in vivo in animal models of diet-induced insulin resistance, and modulation of SR-BI in vitro regulates production of apoB-containing lipoprotein particles. We postulate that apical and/or basolateral SR-BI may play an important role in intestinal chylomicron production and may contribute to chylomicron overproduction normally observed in insulin-resistant states.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ABCG5 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/ABCG8 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD36, http://linkedlifedata.com/resource/pubmed/chemical/Apolipoprotein B-48, http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats, http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acid Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Fructose, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Npc1l1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Slc27a4 protein, mouse
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1522-1547
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
301
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G326-37
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21546579-ATP-Binding Cassette Transporters, pubmed-meshheading:21546579-Animals, pubmed-meshheading:21546579-Antigens, CD36, pubmed-meshheading:21546579-Apolipoprotein B-48, pubmed-meshheading:21546579-Cricetinae, pubmed-meshheading:21546579-Dietary Fats, pubmed-meshheading:21546579-Duodenum, pubmed-meshheading:21546579-Dyslipidemias, pubmed-meshheading:21546579-Fasting, pubmed-meshheading:21546579-Fatty Acid Transport Proteins, pubmed-meshheading:21546579-Fructose, pubmed-meshheading:21546579-Gene Expression, pubmed-meshheading:21546579-Ileum, pubmed-meshheading:21546579-Insulin, pubmed-meshheading:21546579-Insulin Resistance, pubmed-meshheading:21546579-Intestinal Mucosa, pubmed-meshheading:21546579-Jejunum, pubmed-meshheading:21546579-Lipoproteins, pubmed-meshheading:21546579-Male, pubmed-meshheading:21546579-Membrane Transport Proteins, pubmed-meshheading:21546579-Mesocricetus, pubmed-meshheading:21546579-Mice, pubmed-meshheading:21546579-Mice, Inbred C57BL, pubmed-meshheading:21546579-Models, Animal, pubmed-meshheading:21546579-Postprandial Period, pubmed-meshheading:21546579-RNA, Messenger, pubmed-meshheading:21546579-Up-Regulation
pubmed:year
2011
pubmed:articleTitle
Intestinal SR-BI is upregulated in insulin-resistant states and is associated with overproduction of intestinal apoB48-containing lipoproteins.
pubmed:affiliation
Molecular Structure & Function, Research Institute, The Hospital for Sick Children, University of Toronto, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't