Abstract
Decreased plasma apoA-I and HDL-cholesterol concentrations are common abnormalities in insulin resistant subjects with obesity and type 2 diabetes mellitus that increase their risk of cardiovascular disease. HDL metabolism is a complex system: kinetic studies using stable isotope tracers and multicompartmental modelling have provided useful mechanistic insight into its regulation. Dysregulation of HDL metabolism in insulin resistance involves accelerated catabolism HDL particles, containing both apoA-I and apoA-II. In turn, this is largely consequent on hepatic oversecretion of VLDL and expansion in the plasma pool of triglyceride-rich lipoproteins; hepatic steatosis, elevated apoC-III and low adiponectin contribute to these changes. Weight loss and fish oils lower the fractional catabolism of HDL but “balancing feedback”, at least in the short-term, sees a fall in apoA-I production, with no net change in plasma HDL concentration. Rosuvastatin increases apoA-I and HDL-cholesterol concentrations by decreasing the catabolism of HDL-apoA-I. PPAR-α agonists increase apoA-I production and potentially enhance reverse cholesterol transport; this effect has also been described with niacin, but requires confirmation. The differential effects of rosuvastatin and fenofibrate on HDL metabolism provides a good rationale for their use as combination therapy. The clinical significance of lifestyle and pharmacologically induced changes in HDL metabolism must be recognized in the light of parallel improvements in apoB metabolism. New clinical methods are needed for investigating cellular and in vivo cholesterol transport.
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Abbreviations
- Apo:
-
Apolipoprotein
- CETP:
-
Cholesteryl ester transfer protein
- CVD:
-
Cardiovascular disease
- HDL:
-
High-density lipoprotein
- FCR:
-
Fractional catabolic rate
- IDL:
-
Intermediate-density lipoprotein
- LDL:
-
Low-density lipoprotein
- LPL:
-
Lipoprotein lipase
- MetS:
-
Metabolic syndrome
- PPAR:
-
Peroxisome proliferator-activated receptor
- PR:
-
Production rate
- RCT:
-
Reverse cholesterol transport
- TRL:
-
Triglyceride-rich lipoprotein
- VLDL:
-
Very low-density lipoprotein
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Chan, D.C., Barrett, P.H.R., Watts, G.F. (2010). Therapeutic Regulation of High-Density Lipoprotein Transport in the Metabolic Syndrome. In: Schaefer, E. (eds) High Density Lipoproteins, Dyslipidemia, and Coronary Heart Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1059-2_20
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DOI: https://doi.org/10.1007/978-1-4419-1059-2_20
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