We are continuing to use the rat as a model to study the biosynthesis and metabolism of plasma apolipoprotein B (apoB), the structural protein of very low density lipoproteins (VLDL). Evidence has been obtained that perfused rat livers produce three forms of apoB (B-100, B-95 and B-48), differing in their apparent molecular weights. Furthermore, the relative amount of the three forms produced appears to be regulated by diet and perhaps other physiological variables. This seems important because in other studies we have shown that all three forms of apoB are independently metabolized. Together, these findings point to a complex mechanism in the rat whereby the metabolic fate of hepatic VLDL and its lipid component is physiologically regulated by the form of apoB it contains. We have developed a new and simpler method in vivo to measure the relative production rates of the individual forms of apoB. The method is based on the ability of Triton WR-1339, a nonionic detergent given I.V., to block the clearance of pulse-labeled apoB from the circulation. Findings with this method are as follows (all ratios refer to relative production rates): (1) Triton alone reduced B-100/B-95 from 3 to 2 without affecting B-48/(B-100 + B-95). (2) Surgery to implant cannulas in the jugular vein and duo denum, followed by restraint, reduced B-100/B-95 to 1.3 after 18 hours without affecting B-48/(B-100 + B-95). Sham surgery alone had a similar effect after the same time period. (3) Infusing flucose intraduodenally for 18 hours increased B-48/(B-100 + B-95) without affecting B-100/B-95. (4) Fasting for 42 hours decreased B-48/(B-100 + B-95) from 2.9 to 0.7 without affecting B-100/B-95. (5) Taken together these data indicate that B-100/B95 is decreased by physiological stress while B-48/(B-100 + B-95) is regulated by dietary variables.
