Normal triglyceride levels despite insulin resistance in African Americans: Role of lipoprotein lipase

Lipoprotein lipase (LPL), the enzyme responsible for hydrolyzing triglyceride (TG) in plasma lipoproteins, is a key regulator of plasma TG levels. In Caucasians, postheparin-LPL (PH-LPL) activity is impaired in the presence of insulin resistance and leads to elevated TG levels. However, African Americans are often both insulin-resistant and normotriglyceridemic. But in African Americans, the effect of insulin resistance on PH-LPL activity has not been studied. In African Americans, if insulin resistance is not associated with a decrease in PH-LPL activity, this could account for the simultaneous presence of insulin resistance and normotriglyceridemia. Therefore, our goal was to determine in African Americans the relationship between insulin resistance and PH-LPL activity. In a cross-sectional study of 107 nondiabetic African Americans (57 men and 50 women; age mean ± SD, 35 ± 8 years, range 22-50 years; body mass index 31.6 ± 7.9 kg/m², range 18.5-54.7 kg/m²), fasting TG levels and PH-LPL activity were determined. Visceral adipose tissue was measured by abdominal computed tomographic scan. Insulin resistance was determined by the insulin sensitivity index (S _I). Subjects were divided into tertiles by S_I. The range of S_I in each tertile was 12.75 to 3.99, 3.87 to 2.20, 2.06 to 0.17 mU • L^-1 • min^-1. Insulin resistance was defined as being in the third tertile. TG levels in the men and women were 82.2 ± 35.5 versus 56.4 ± 30.1 mg/dL, P <. 001. There were no sex difference in PH-LPL activity (8.9 ± 2.5 vs 9.6 ± 3.2 mmol/h per liter, P =. 30) or S_I (3.65 ± 2.59 vs 3.23 ± 1.89 L • mU^-1 • min^-1, P =. 49). Although 47% of the subjects were obese, only 4% of subjects had hypertriglyceridemia (TG ≥ 150 mg/dL). By 2 separate analyses, PH-LPL was a major determinant of TG levels. First, there was a significant inverse correlation between PH-LPL activity and TG levels (men: r = -0.46, P <. 001; women: r = -0.28, P =. 046). Second, in the multiple regression analysis with TG as the dependent variable and PH-LPL, age, sex, S_I, and visceral adipose tissue as independent variables, adjusted R² was 54% and the effect of PH-LPL on TG levels was highly significant(P <. 001). However, insulin resistance did not appear to influence PH-LPL activity. This is demonstrated in 3 ways: first, PH-LPL activity was not different in the S_I tertiles (9.10 ± 2.75, 9.52 ± 2.91, 9.13 ± 2.89 mmol/h per liter, P =. 78); the correlation between PH-LPL and S_I was not significant (men: r = 0.09, P =. 51; women: r = -0.03, P =. 78), and a multiple regression with PH-LPL as the dependent variable and age, S_I, body mass index, and sex as independent variables, adjusted R² was <2% and the contribution of S_I was not significant (P =. 53). Hence, in African Americans, increased PH-LPL activity is associated with a decrease in TG levels. The lack of an effect of insulin resistance on PH-LPL could allow LPL to clear TG even in the presence of insulin resistance and explain the coexistence of insulin resistance and normotriglyceridemia in African Americans.