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

Department of Clinical Chemistry, Staffordshire General Hospital, Stafford, UK.
Atherosclerosis (Impact Factor: 3.99). 04/2008; 197(1):164-70. DOI: 10.1016/j.atherosclerosis.2007.03.009
Source: PubMed


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.
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.
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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    • "However, other authors showed that VLDL increase in FCH patients is mainly related to defects in activity of lipoprotein lipase (Campagna et al 2002), lecithin:cholesterol acyltransferase (Aouizerat et al 2002), and/or hepatic lipase (Pihlajamaki et al 2000). On the other hand, Evans et al (2007) recently used stable isotope techniques combined with tissue-specifi c measurements in adipose tissue and forearm muscle to investigate fatty acid handling by these tissues in the fasting and postprandial states of FCH patients. They found that the major defect appeared to be overproduction of triacylglycerol (TAG) by the liver due to decreased fatty acid oxidation, with fatty acids directed to TG synthesis, while evidence of decreased lipoprotein lipase action or impaired fatty acid re-esterifi cation in adipose tissue was observed. "
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