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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.

Original publication

DOI

10.1016/j.atherosclerosis.2007.03.009

Type

Journal article

Journal

Atherosclerosis

Publication Date

03/2008

Volume

197

Pages

164 - 170

Keywords

3-Hydroxybutyric Acid, Adipose Tissue, Adult, Apolipoproteins B, Blood Glucose, Carbon Isotopes, Cholesterol, VLDL, Chylomicrons, Esterification, Fatty Acids, Nonesterified, Female, Humans, Hyperlipidemia, Familial Combined, Insulin, Lipid Metabolism, Liver, Male, Middle Aged, Postprandial Period, Regional Blood Flow