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. (2007) 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).


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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

Item Type: Article
Digital Object Identifier (DOI): doi:10.1016/j.atherosclerosis.2007.03.009
ISSNs: 0021-9150 (print)
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
Subjects: Q Science > QP Physiology
ePrint ID: 61105
Date :
Date Event
26 April 2007e-pub ahead of print
March 2008Published
Date Deposited: 02 Sep 2008
Last Modified: 16 Apr 2017 17:31
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/61105

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