Tumor-induced alterations in hepatic malic enzyme and carnitine palmitoyltransferase activity.
To better understand the role of the liver in the hypertriglyceridemia observed in a tumor-bearing state, we have examined tumor-induced alterations in hepatic lipogenesis and fatty acid oxidation. The effects of differing tumor burden as well as tumor excision on the activity and mRNA levels of malic enzyme and carnitine palmitoyltransferase were studied in Fisher 344 rats bearing a methylcholanthrene-induced sarcoma. Serum triacylglycerols and plasma nonesterified fatty acids (NEFA) levels were both elevated with increasing tumor burden (P < 0.05 vs control). The elevation disappeared with tumor removal. Malic enzyme activity of tumor bearers, compared with control rats, declined with an increase in tumor burden. These two variables were negatively correlated (r = -0.90, P < 0.01). The changes in activity were accompanied by positively correlated changes in mRNA levels (r = 0.73, P < 0.01). Carnitine palmitoyltransferase activity was not altered, even in the presence of a large tumor burden. Hepatic lipogenesis, reflected by malic enzyme activity, was tumor-dependent and was significantly reduced during the period of circulating hypertriglyceridemia. Fatty acid oxidation, reflected by carnitine palmitoyltransferase activity, was not enhanced in spite of an ample supply of NEFAs to the liver from the peripheral tissues. The data suggest that neither hepatic lipogenesis nor fatty acid oxidation contribute to hypertriglyceridemia in the tumor-bearing state.
Noguchi
Y
Y
Surgical Metabolism Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Vydelingum
N A
NA
Brennan
M F
MF
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000201:enzymology*; D014280:Triglycerides / Q000097:blood
D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D014280:Triglycerides; D008748:Methylcholanthrene; D008291:Malate Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase