Impact of obesity in primary hyperlipidemias

Obesity is frequently associated with high plasma triglyceride and reduced plasma high-density lipoprotein (HDL)-cholesterol (HDL-C) levels, and an increased concentration of apoB-carrying lipoproteins. The effects of obesity on lipid metabolism are mainly mediated by insulin resistance and, as central (visceral) obesity significantly increases insulin resistance, it aggravates these lipid changes. We have reviewed the impact of obesity on lipid metabolism in different types of primary hyperlipidemias. Obesity is not common in primary (familial and polygenic) hypercholesterolemias, and insulin resistance is infrequent; various investigators have found no or only a weak association between plasma cholesterol concentrations and insulin levels. On the other hand, in familial hypertriglyceridemia (type IV) and familial combined hyperlipidemia (FCH), obesity and insulin resistance are common and, when present, contribute to a further deterioration in the lipid profile. Weight loss in most of these patients is accompanied by a significant decrease in plasma triglyceride levels and an increase in HDL-C. Reviewing the data published by our group, we show that insulin resistance is an important component of the metabolic derangement in FCH subjects; high fasting plasma free fatty acids and triglycerides levels correlate to insulin resistance, thus linking this abnormality to lipid metabolism. A high waist/hip ratio (indicating visceral fat deposits) exacerbates insulin resistance, but this is also present in lean FCH subjects. Furthermore, insulin resistance is associated with a higher prevalence of coronary heart disease in this group of subjects.