Lipid kinetic alterations in tumor-bearing rats: reversal by tumor excision.

Overview

Cancer cachexia is frequently accompanied by hyperlipidemia. To identify the mechanisms underlying this alteration in lipid metabolism, free fatty acid (FFA) and very low density lipoprotein-associated triacylglycerol (VLDL-TG) kinetics were determined in tumor-bearing (subcutaneously implanted methylcholanthrene-induced sarcoma) Fischer 344 rats. The animals were studied after chronic vascular catheterization, in an unanesthetized, undisturbed state, after 24 hr of fasting. They were separated into three groups: control (n = 5), tumor-bearing (n = 5, tumor burden = 10% body weight), and 7 days after tumor excision (n = 5). VLDL-TG and FFA kinetics were assessed by a constant infusion of [3H]palmitate-labeled VLDL-TG and [14C]palmitate bound to albumin, respectively. FFA rate of appearance (FFA-Ra) and clearance (FFA-Cl) and VLDL-TG rate of appearance (VLDL-TG-Ra) and clearance (VLDL-TG-Cl) were determined at steady state. We observed that the tumor-bearing rats had significantly increased FFA-Ra and VLDL-TG-Ra, decreased VLDL-CL, and maintained FFA-Cl, when compared to control. These alterations returned to normal levels after tumor excision. The results suggest that the hyperlipidemia observed in tumor-bearing rats is due to elevated lipolysis rate, maintained rate of plasma FFA clearance, increased triacylglycerol production and VLDL secretion by the liver, and decreased VLDL-TG clearance from plasma. These alterations were reversed 7 days following tumor excision.