Decrease in malonyl-CoA and its background metabolic alterations in murine model of cancer cachexia.
The alterations of enzymatic activities involved in lipid degradation in cancer cachexia have not been fully elucidated. One of the two subclones of colon 26 adenocarcinoma, clone 20, with a potent ability to induce cachexia, or clone 5, without such an activity, was transplanted in to CDF-1 male mice. Murine livers were extirpated for analyses on the 14th day after tumor inoculation. The body weights and food intake of mice bearing clone 20 were all significantly lower than those of non-tumor bearing mice and mice bearing the clone 5 tumor. The decline of body weight was accompanied by a shrinkage of epididymal fat pads. Expression of spermidine/spermine N-1 acetyl transferase (SSAT) assessed by real-time PCR was significantly increased in cachectic mice. Conversely, acetyl-CoA carboxylase (ACC) measured by Western blotting and malonyl-CoA levels determined by malonyl-CoA:acetyl-CoA cycling procedures were decreased in cachectic mice. Indomethacin in drinking water reversed the clone 20 induced decrease in body and fat weight and food intake, and simultaneously negated the clone 20 induced increase of SSAT expressions and decrease of ACC and malonyl-CoA amounts. Because malonyl-CoA inhibits the rate-limiting step in the beta-oxidation of fatty acids, the decreased malonyl-CoA and the background metabolic alterations may contribute to the accelerated lipolysis of cancer cachexia.
Celik
Alper
A
Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Kano
Yoshihiko
Y
Tsujinaka
Shingo
S
Okada
Sinichirou
S
Takao
Koichi
K
Takagi
Masakazu
M
Chohnan
Shigeru
S
Soda
Kuniyasu
K
Kawakami
Masanobu
M
Konishi
Fumio
F
D000103:Acetyl-CoA Carboxylase / Q000032:analysis / Q000235:genetics; D000123:Acetyltransferases / Q000235:genetics; D000818:Animals; D001835:Body Weight; D002100:Cachexia / Q000378:metabolism*; D004195:Disease Models, Animal; D004435:Eating; D008099:Liver / Q000378:metabolism; D008297:Male; D008316:Malonyl Coenzyme A / Q000032:analysis* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009369:Neoplasms / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D000099228:Diamine N-Acetyltransferase
D000103:Acetyl-CoA Carboxylase; D000123:Acetyltransferases; D008316:Malonyl Coenzyme A; D000099228:Diamine N-Acetyltransferase