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Tissue-specific stable isotope measurements of postprandial lipid metabolism in familial combined hyperlipidaemia

Evans, Kevin, Burdge, Graham C., Wootton, Stephen A., Collins, Jenny M., Clark, Mo L., Tan, Garry D., Karpe, Frederik and Frayn, Keith N. (2008) Tissue-specific stable isotope measurements of postprandial lipid metabolism in familial combined hyperlipidaemia Atherosclerosis, 197, (1), pp. 164-170. (doi:10.1016/j.atherosclerosis.2007.03.009). (PMID:17466309).

Record type: Article


Objective: The metabolic defects underlying familial combined hyperlipidaemia (FCHL) are not clearly understood. We used stable isotope techniques combined with tissue-specific measurements in adipose tissue and forearm muscle to investigate fatty acid handling by these tissues in the fasting and postprandial states.

Results: Patients were insulin resistant as shown by higher glucose and insulin concentrations and lower muscle glucose extraction than controls. Plasma triacylglycerol (TAG) concentrations were higher in patients. Adipose tissue TAG extraction was not lower in patients than controls, although TAG clearance was lower, probably representing saturation. Following a test meal, patients showed a greater increase in chylomicron-TAG concentrations. There were no differences between FCHL patients and controls in postprandial suppression of non-esterified fatty acid (NEFA) concentrations or postprandial NEFA release, but patients had greater trapping of exogenous fatty acids in adipose tissue. 3-Hydroxybutyrate concentrations were lower in patients indicative of decreased hepatic fatty acid oxidation.

Conclusions: In this group of patients with FCHL, the major defect appeared to be overproduction of TAG by the liver due to decreased fatty acid oxidation, with fatty acids directed to TAG synthesis. We found no evidence of decreased lipoprotein lipase action or impaired fatty acid re-esterification in adipose tissue

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e-pub ahead of print date: 26 April 2007
Published date: March 2008
Keywords: adipose-tissue, vldl, middle aged, cholesterol, insulin, humans, fatty acids, female, blood glucose, research, diagnostic use, liver, esterification, fasting, apolipoproteins b, male, adult, glucose, nonesterified, diagnosis, regional blood flow, muscle, fatty acid, chemistry, lipid metabolism, chylomicrons, metabolism, 3-hydroxybutyric acid, postprandial period, adipose tissue, plasma, hyperlipidemia, carbon isotopes, familial combined, blood, acid


Local EPrints ID: 61105
ISSN: 0021-9150
PURE UUID: cab1bed0-bfe8-4401-9f62-6409b8135d6f
ORCID for Graham C. Burdge: ORCID iD

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Date deposited: 02 Sep 2008
Last modified: 17 Jul 2017 14:22

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Author: Kevin Evans
Author: Jenny M. Collins
Author: Mo L. Clark
Author: Garry D. Tan
Author: Frederik Karpe
Author: Keith N. Frayn

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