Effect of lipoprotein lipase activators bezafibrate and NO-1886, on B16 melanoma-induced cachexia in mice.
Our recent study has demonstrated that B16 melanoma-induced cachexia in mice is inhibited by ponalrestat, an aldose reductase inhibitor, which has the ability to activate lipoprotein lipase (LPL) activity both in vitro and in vivo. In this study, the effect of bezafibrate and NO-1886, LPL activators, on B16 melanoma-induced cachectic symptoms was investigated in mice. Treatment with bezafibrate resulted in an attenuation of the decrease in the weight of epididymal fat and whole body lipid observed in mice following intraperitoneal inoculation of B16. The increase in the levels of triglyceride and non-esterified fatty acid, and a decrease in the level of glucose in the blood, which was induced by the presence of tumor, were also restored to that of normal mice after treatment with bezafibrate. The reduction in the weight of epididymal fat and whole body lipid induced by B16 was also ameliorated by NO-1886. Overall, this study demonstrated that cachexia induced by B16 melanoma in mice was alleviated by the LPL activators bezafibrate and NO-1886, suggesting the involvement of the impaired LPL activity in the establishment of cachexia syndrome in mice bearing B16 melanoma.
Kawamura
I
I
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. ikuo_kawamura@po.fujisawa.co.jp
Yamamoto
N
N
Sakai
F
F
Yamazaki
H
H
Goto
T
T
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001629:Bezafibrate / Q000494:pharmacology*; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D002784:Cholesterol / Q000378:metabolism; D020536:Enzyme Activators / Q000494:pharmacology*; D004822:Epididymis / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D008546:Melanoma, Experimental / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D001549:Benzamides; D020536:Enzyme Activators; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D009943:Organophosphorus Compounds; D014280:Triglycerides; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D002784:Cholesterol; D008071:Lipoprotein Lipase; D005947:Glucose; D001629:Bezafibrate