Pharmacological Regulation of Fat Transport in Metabolic Syndrome

Regulation of Lipoprotein Kinetics by Atorvastatin and Fenofibrate With the Metabolic Syndrome

The purpose of this study is to determine whether atorvastatin and fenofibrate are effective in the treatment of lipid disorders in obese, insulin resistant subjects.

Insulin resistance is a heterogeneous metabolic disorder of complex etiology. It underpins dyslipoproteinemia, a key feature of the metabolic syndrome (MetS) that independently predicts cardiovascular disease (CVD). Hypertriglyceridemia, the most consistent lipid disorder in subjects with obesity and type 2 diabetes mellitus, is chiefly a consequence of overproduction and delayed clearance of triglyceride-rich lipoproteins (TRLs). Although the precise mechanisms involved are incompletely understood, experimental and clinical evidence suggests that elevated apolipoprotein (apo) C-III may play a crucial role in the dysregulation of TRL metabolism. investigating the effects of these agents on VLDL-apoC-III kinetics. In this study, we aimed to examine the effect of two lipid-regulating agents, atorvastatin and fenofibrate on VLDL-apoC-III transport. We hypothesized that atorvastatin and fenofibrate would have similar effects on apoC-III transport by decreasing the production and increasing the catabolism of VLDL-apoC-III.

Inclusion Criteria:

any three of the followings

• waist circumference >102cm
• triglycerides >1.7 mmol/L
• HDL-cholesterol <1.05 mmol/L
• blood glucose >6.1 mmol/L
• blood pressure >130/85mmHg

Exclusion Criteria:

• plasma cholesterol >7mmo/L
• triglycerides >4.5mmo/L
• diabetes mellitus (defined by oral glucose tolerance test)
• CVD
• consumption of >30g alcohol/day
• use of agents affecting lipid metabolism
• APOE2/E2 genotype, macroproteinuria
• creatinaemia (>120umol/L)
• hypothyroidism
• abnormal liver and muscle enzymes.