The concurrence of visceral obesity, insulin resistance and dyslipidaemia comprises the concept of the metabolic syndrome. The metabolic syndrome is an escalating problem in developed and developing societies that tracks with the obesity epidemic. Dyslipidaemia in the metabolic syndrome is potently atherogenic and, hence, is a major risk factor for CVD (cardiovascular disease) in these subjects. It is globally characterized by hypertriglyceridaemia, near normal LDL (low-density lipoprotein)-cholesterol and low plasma HDL (high-density lipoprotein)-cholesterol. ApoC-III (apolipoprotein C-III), an important regulator of lipoprotein metabolism, is strongly associated with hypertriglyceridaemia and the progression of CVD. ApoC-III impairs the lipolysis of TRLs [triacylglycerol (triglyceride)-rich lipoproteins] by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors. In the circulation, apoC-III is associated with TRLs and HDL, and freely exchanges among these lipoprotein particle systems. However, to fully understand the complex physiology and pathophysiology requires the application of tracer methodology and mathematical modelling. In addition, experimental evidence shows that apoC-III may also have a direct role in atherosclerosis. In the metabolic syndrome, increased apoC-III concentration, resulting from hepatic overproduction of VLDL (very-LDL) apoC-III, is strongly associated with delayed catabolism of triacylglycerols and TRLs. Several therapies pertinent to the metabolic syndrome, such as PPAR (peroxisome-proliferator-activated receptor) agonists and statins, can regulate apoC-III transport in the metabolic syndrome. Regulating apoC-III metabolism may be an important new therapeutic approach to managing dyslipidaemia and CVD risk in the metabolic syndrome.

The metabolic syndrome is characterized by insulin resistance and abnormal apolipoprotein AI (apoAI) and apolipoprotein B-100 (apoB) metabolism that may collectively accelerate atherosclerosis. The effects of atorvastatin (40 mg/day) and micronised fenofibrate (200 mg/day) on the kinetics of apoAI and apoB were investigated in a controlled cross-over trial of 11 dyslipidemic men with the metabolic syndrome. ApoAI and apoB kinetics were studied following intravenous d 3 -leucine administration using gas-chromatography mass spectrometry with data analyzed by compartmental modeling. Compared with placebo, atorvastatin significantly decreased (P < 0.001) plasma concentrations of cholesterol, triglyceride, LDL cholesterol, VLDL apoB, intermediate-density lipoprotein (IDL) apoB, and LDL apoB. Fenofibrate significantly decreased (P < 0.001) plasma triglyceride and VLDL apoB and elevated HDL 2 cholesterol (P < 0.001), HDL 3 cholesterol (P < 0.01), apoAI (P ‫؍‬ 0.01), and apoAII (P < 0.001) concentrations, but it did not significantly alter LDL cholesterol. Atorvastatin significantly increased (P < 0.002) the fractional catabolic rate (FCR) of VLDL apoB, IDL apoB, and LDL apoB but did not affect the production of apoB in any lipoprotein fraction or in the turnover of apoAI. Fenofibrate significantly increased (P < 0.01) the FCR of VLDL, IDL, and LDL apoB but did not affect the production of VLDL apoB. Relative to placebo and atorvastatin, fenofibrate significantly increased the production (P < 0.001) and FCR (P ‫؍‬ 0.016) of apoAI. Both agents significantly lowered plasma triglycerides and apoCIII concentrations, but only atorvastatin significantly lowered (P < 0.001) plasma cholesteryl ester transfer protein activity. Neither treatment altered insulin resistance. In conclusion, these differential effects of atorvastatin and fenofibrate on apoAI and apoB kinetics support the use of combination therapy for optimally regulating dyslipoproteinemia in the metabolic syndrome. Diabetes 52:803-811, 2003

In men WC is the anthropometric index that most uniformly predicts the distribution of adipose tissue among several fat compartments in the abdominal region, there apparently being little value in measuring WHR or BMI.

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