Influence of DMBA-induced mammary cancer on the liver CPT I, mit HMG-CoA synthase and PPARalpha mRNA expression in rats fed a low or high corn oil diet.
Hepatic mitochondrial outer membrane carnitine palmitoyltransferase I (CPT I) and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) enzymes play a key role in regulation of fatty acid oxidation and in ketogenic pathways, respectively. Their expression are regulated by fatty acids mainly by the peroxisome proliferator-activated receptor alpha (PPARalpha). To investigate possible mechanisms through which cancer alters the lipid metabolism, we analyzed by Northern blot, the mRNA relative abundance of these proteins in liver from healthy and DMBA-induced mammary tumor-bearing rats fed a low or high corn oil diet. Serum levels of lipids, body weight and mass were also determined. Whereas mRNA steady-state levels of CPT I and mit HMG-CoA synthase were unaffected by the presence of the extra-hepatic tumor, the cancer state seemed to modify the regulation of the expression of these genes by high fat diet. We hypothesize that putative changes in PPARalpha mRNA levels could have contributed to such alterations. These results, together with changes in serum lipid profiles, body weight and mass, indicate fat mobilization and non-enhanced oxidation rates despite a high-fat feeding. This effect of the cancer state could be related to tumor aggressiveness and suggest a preferential redirection of long-chain fatty acids into energetic and specific pathways of the cancer cells.
Moral
Raquel
R
Department of Cell Biology, Physiology and Immunology, Medical Physiology Unit, School of Medicine, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Solanas
Montserrat
M
Manzanares
Eva Mónica
EM
Haro
Diego
D
Escrich
Eduard
E
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight; D002273:Carcinogens; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis*; D003066:Coenzyme A Ligases / Q000096:biosynthesis*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006904:Hydroxymethylglutaryl-CoA Synthase; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000201:enzymology*; D009369:Neoplasms / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D047493:PPAR alpha / Q000096:biosynthesis* / Q000378:metabolism; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D005227:Fatty Acids; D008055:Lipids; D047493:PPAR alpha; D012333:RNA, Messenger; D015127:9,10-Dimethyl-1,2-benzanthracene; D012313:RNA; D002334:Carnitine O-Palmitoyltransferase; D006904:Hydroxymethylglutaryl-CoA Synthase; D003066:Coenzyme A Ligases; D010100:Oxygen