Tissue-specific stable isotope measurements of postprandial lipid metabolism in familial combined hyperlipidaemia
ABSTRACT 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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ABSTRACT: Accurate assessment of fat intake is essential to examine the relationships between diet and disease risk but the process of estimating individual intakes of fat quality by dietary assessment is difficult. Tissue and blood fatty acids, because they are mainly derived from the diet, have been used as biomarkers of dietary intake for a number of years. We review evidence from a wide variety of cross-sectional and intervention studies and summarise typical values for fatty acid composition in adipose tissue and blood lipids and changes that can be expected in response to varying dietary intake. Studies in which dietary intake was strictly controlled confirm that fatty acid biomarkers can complement dietary assessment methodologies and have the potential to be used more quantitatively. Factors affecting adipose tissue and blood lipid composition are discussed, such as the physical properties of triacylglycerol, total dietary fat intake and endogenous fatty acid synthesis. The relationship between plasma lipoprotein concentrations and total plasma fatty acid composition, and the use of fatty acid ratios as indices of enzyme activity are also addressed.Progress in Lipid Research 10/2008; 47(5):348-80. DOI:10.1016/j.plipres.2008.03.003 · 12.96 Impact Factor
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ABSTRACT: An upper body/visceral fat distribution in obesity is closely linked with metabolic complications, whereas increased lower body fat is independently predictive of reduced cardiovascular risk. The measured functions of different fat depots with regards to fatty acid storage and release in health and obesity were reviewed. The adverse effects of experimentally increasing free fatty acid (FFA) concentrations on liver, muscle, pancreatic beta-cell, and endothelial function were noted. The most dramatic abnormality in FFA metabolism is failure to suppress FFA concentrations/adipose tissue lipolysis normally in response to postprandial hyperinsulinemia. Upper body sc fat delivers the majority of FFA to the systemic circulation under postabsorptive and postprandial conditions. In upper body obesity, portal FFA concentrations resulting from both systemic and visceral adipose tissue lipolysis may be significantly greater than arterial FFA concentrations, exposing the liver to even greater amounts of FFA. Visceral fat also releases sufficient IL-6 to increase portal vein IL-6 concentrations, which can affect hepatic metabolism as well. Lower body, upper body sc, and visceral fat depots have unique characteristics with regards to fatty acid metabolism. Selective dysregulation of these depots probably plays an important role with the metabolic complications of obesity.Journal of Clinical Endocrinology & Metabolism 11/2008; 93(11 Suppl 1):S57-63. DOI:10.1210/jc.2008-1585 · 6.31 Impact Factor
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ABSTRACT: This review summarizes the progress made in cutting through the biological and genetic complexity of the Gordian knot that is familial combined hyperlipidemia. We particularly focus on how the application of new genomic technologies, especially massively parallel sequencing and high-throughput genotyping platforms, promise to accelerate the gene discovery process in this common, highly atherogenic disorder, with important diagnostic and therapeutic implications.The Journal of Lipid Research 12/2008; 50 Suppl:S370-5. DOI:10.1194/jlr.R800081-JLR200 · 4.73 Impact Factor