Linked Life Data

15878874

Source:http://linkedlifedata.com/resource/pubmed/id/15878874

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
27
pubmed:dateCreated
2005-7-4
pubmed:abstractText
In vitro studies suggest that the mitochondrial glycerol-3-phosphate acyltransferase-1 (mtGPAT1) isoform catalyzes the initial and rate-controlling step in glycerolipid synthesis and aids in partitioning acyl-CoAs toward triacylglycerol synthesis and away from degradative pathways. To determine whether the absence of mtGPAT1 would increase oxidation of acyl-CoAs and restrict the development of hepatic steatosis, we fed wild type and mtGPAT1-/- mice a diet high in fat and sucrose (HH) for 4 months to induce the development of obesity and a fatty liver. Control mice were fed a diet low in fat and sucrose (LL). With the HH diet, absence of mtGPAT1 resulted in increased partitioning of acyl-CoAs toward oxidative pathways, demonstrated by 60% lower hepatic triacylglycerol content and 2-fold increases in plasma beta-hydroxybutyrate, acylcarnitines, and hepatic mRNA expression of mitochondrial HMG-CoA synthase. Despite the increase in fatty acid oxidation, liver acyl-CoA levels were 3-fold higher in the mtGPAT1-/- mice fed both diets. A lack of difference in CPT1 and FAS mRNA expression between genotypes suggested that the increased acyl-CoA content was not because of increased de novo synthesis, but instead, to an impaired ability to use long-chain acyl-CoAs derived from the diet, even when the dietary fat content was low. Hyperinsulinemia and reduced glucose tolerance on the HH diet was greater in the mtGPAT1-/- mice, which did not suppress the expression of the gluconeogenic genes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. This study demonstrates that mtGPAT1 is essential for normal acyl-CoA metabolism, and that the absence of hepatic mtGPAT1 results in the partitioning of fatty acids away from triacylglycerol synthesis and toward oxidation and ketogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25629-36
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15878874-Animals, pubmed-meshheading:15878874-Carnitine, pubmed-meshheading:15878874-Coenzyme A, pubmed-meshheading:15878874-Dietary Fats, pubmed-meshheading:15878874-Dietary Sucrose, pubmed-meshheading:15878874-Fatty Liver, pubmed-meshheading:15878874-Female, pubmed-meshheading:15878874-Glycerol-3-Phosphate O-Acyltransferase, pubmed-meshheading:15878874-Insulin Resistance, pubmed-meshheading:15878874-Ketones, pubmed-meshheading:15878874-Lipids, pubmed-meshheading:15878874-Liver, pubmed-meshheading:15878874-Lysophospholipids, pubmed-meshheading:15878874-Male, pubmed-meshheading:15878874-Mice, pubmed-meshheading:15878874-Mice, Inbred C57BL, pubmed-meshheading:15878874-Mice, Knockout, pubmed-meshheading:15878874-Mitochondria, pubmed-meshheading:15878874-Obesity, pubmed-meshheading:15878874-Oxidation-Reduction, pubmed-meshheading:15878874-Triglycerides, pubmed-meshheading:15878874-Weight Gain
pubmed:year
2005
pubmed:articleTitle
Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential in liver for the metabolism of excess acyl-CoAs.
pubmed:affiliation
Department of Nutrition, University of North Carolina, North Chapel Hill, Carolina 27599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural