Hepatic production of VLDL1 but not VLDL2 is related to insulin resistance in normoglycaemic middle-aged subjects.

Insulin resistance is probably the defining feature of the metabolic syndrome and is an important determinant of plasma triglyceride (TG) concentrations. We sought to investigate whether insulin resistance influenced the metabolism of VLDL1 (Sf 60-400) and VLDL2 (Sf 20-60). Sixteen (eight men, eight women) middle-aged, normoglycaemic subjects participated. VLDL1and VLDL2 apolipoprotein (apo) B metabolism was followed using a deuterated leucine tracer and insulin resistance was estimated using homeostasis model assessment (HOMA). HOMA-estimated insulin resistance (HOMAIR) significantly and strongly correlated with the VLDL1 production rate (r = 0.69, P < 0.01) and VLDL1 apo B pool size (r = 0.59, P = 0.02), but these relationships were not evident for VLDL2. Conversely, HOMAIR was not significantly related to the fractional rate of transfer of VLDL1 to VLDL2 but was significantly related to the fractional rate of transfer from VLDL2 to IDL (r = 0.61, P = 0.01). HOMAIR was not significantly related to the fractional rate of direct catabolism for either VLDL1 or VLDL2. These results suggest a role for insulin resistance in the determination of hepatic VLDL1 production and highlight the independent regulation of VLDL1 and VLDL2 metabolism.

Effects of dietary monounsaturated fatty acids on lipoprotein concentrations, compositions, and subfraction distributions and on VLDL apolipoprotein B kinetics: dose-dependent effects on LDL.

BACKGROUND: Replacing dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) lowers LDL cholesterol, but the underlying mechanisms remain unclear. OBJECTIVE: We assessed the effects of replacing dietary SFAs with MUFAs on concentrations and subclass distributions of VLDL, intermediate-density lipoprotein, LDL, and HDL and on VLDL apolipoprotein B kinetics. DESIGN: Thirty-five moderately hypercholesterolemic, middle-aged volunteers consumed for 6 wk, in random order, diets containing low (L-MUFA; 7.8% of energy from MUFAs), moderate (M-MUFA; 10.3% from MUFAs), or high (H-MUFA; 13.7% from MUFAs) amounts of MUFAs. Fasting blood samples were taken from all subjects after each intervention. VLDL apolipoprotein B kinetic studies were performed in a subgroup after the L-MUFA and H-MUFA diets. RESULTS: Plasma cholesterol concentrations decreased in a dose-dependent manner with increasing intakes of dietary MUFAs. This change was entirely accounted for by reduced LDL cholesterol (-0.20 and -0.49 mmol/L after the M-MUFA and H-MUFA diets, respectively, compared with the concentration after the L-MUFA diet; P for trend < 0.01). Plasma triacylglycerol and HDL cholesterol were not significantly affected by the dietary intervention, nor were the concentrations of VLDL(1) (S(f) 60-400), VLDL(2) (S(f) 20-60), or intermediate-density lipoprotein (S(f) 12-20). Production and catabolic rates for VLDL(1) and VLDL(2) were also unaffected. HDL and LDL subclass distributions were not significantly altered, but as a consequence of the overall LDL lowering, concentrations of atherogenic LDL-III were 25% lower after the H-MUFA diet than after the L-MUFA diet (P = 0.02). CONCLUSION: The effects of replacing dietary SFAs with MUFAs on lipoprotein metabolism appear to be almost exclusively limited to the LDL density class.