Bile acid kinetics in relation to endogenous tryglyceride metabolism in various types of hyperlipoproteinemia.

Abstract

Bile acid and plasma endogenous triglyceride kinetics were determined under standardized dietary conditions in 47 hyperlipidemic subjects with the aid of [14C]cholic acid, [14C]chenodeoxycholic acid, and [3H]glycerol, respectively. On the basis of their lipoprotein pattern the patients were separated into three groups characterized by hyperlipoproteinemia (HLP) type IIa (n = 19), type IIb (n = 6), and type IV (n = 22). In keeping with previous reports from this laboratory the total bile acid formation reports from this laboratory the total bile acid formation in HLP type IV (19.5 +/- 2.2) mumol kg-1d-1, mean +/- SEM) exceeded that encountered in type IIa (10.7 +/- 0.9 mumol kg-1d-1, P less than 0.005). This difference was mainly due to an increased synthesis of cholic acid in type IV HLP (12.7 +/- 1.7 mumol kg-1d-1 vs. 6.1 +/- 0.5 mumol kg-1d-1, P less than 0.005). Bile acid formation in type IIb HLP was essentially within the limits recorded for type IIa. Apparent plasma triglyceride formation (as calculated from the 10-hr radioactivity decay curve) averaged 10.5 +/- 0.7 mumol kg-1hr-1 in type IIa HLP and was significantly higher in type IIb (20.7 +/- 1.9 mumol kg-1hr-1, P less than 0.001) and in type IV (22.1 +/- 1.4 mumol kg-1hr-1, P less than 0.001). The apparent fractional turnover rate of plasma triglyceride in type IV HLP (0.147 +/- 0.011 hr-1) was lower than that encountered in type IIa (0.188 +/- 0.008, P less than 0.01) and in type IIb (0.177 +/- 0.011 hr-1). The apparent production of plasma triglycerides and the formation of cholic acid correlated in type IIa (r = +0.69, P less than 0.001) and in type IV HLP (r = +0.70, P less than 0.001). A similar pattern was seen for total bile acid formation, while chenodeoxycholic acid showed a correlation to apparent triglyceride synthesis only in type IV HLP. It is suggested that an increased formation of plasma triglycerides–monitoring very low density lipoprotein synthesis–is linked to an enhanced degradation of cholesterol to bile acids and that there is an integrated regulation of the metabolism of these two parameters.