A Mediterranean-style, low-glycemic-load diet reduces the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in mononuclear cells and plasma insulin in women with metabolic syndrome

Abstract

We evaluated changes in low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase gene expression in women with metabolic syndrome and elevated plasma LDL cholesterol (LDL-C). We hypothesized that expression of these 2 genes would be modulated by our dietary intervention. Twenty-five women were instructed to follow a Mediterranean-style low-glycemic-load diet for 12 weeks. Quantitative real-time polymerase chain reaction was used to measure messenger RNA (mRNA) abundance of the LDL receptor and HMG-CoA reductase in mononuclear cells, which were used as a proxy of liver expression of these 2 genes. All women experienced favorable impacts on metabolic syndrome variables, with decreases in waist circumference (P < .001), plasma triglycerides (P < .05), and systolic blood pressure (P < .05) compared with baseline. Furthermore, participants had reductions in LDL-C (P < .01), plasma insulin (P < .001), and homeostatic model assessment score for insulin resistance (P < .001) over time. In addition, significant decreases were found in plasma tumor necrosis factor α (P < .01), which might have contributed to the improvements observed in insulin resistance. Although no changes in LDL-receptor mRNA levels were observed, HMG-CoA-reductase gene expression was reduced (P < .001) after 12 weeks. The reductions in plasma insulin correlated with changes in HMG-CoA-reductase mRNA levels (r = 0.45, P < .01). In conclusion, the observed reductions in plasma insulin may have affected the expression of a key regulatory gene of cholesterol synthesis, HMG-CoA reductase. The decreased HMG-CoA-reductase expression may be related to lower secretion of very low density lipoprotein (VLDL)-cholesterol, which, in turn, would account for the reductions in LDL-C.