Lipid kinetic alterations in tumor-bearing rats: reversal by tumor excision.
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.
Younes
R N
RN
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Vydelingum
N A
NA
Noguchi
Y
Y
Brennan
M F
MF
D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007700:Kinetics; D050356:Lipid Metabolism; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D009994:Osmolar Concentration; D011184:Postoperative Period; D051381:Rats; D011916:Rats, Inbred F344; D012513:Sarcoma, Experimental / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D014280:Triglycerides / Q000097:blood
D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D014280:Triglycerides