Hypertriglyceridemia associated with tumor necrosis factor-alpha in hamster cheek-pouch carcinogenesis.
We demonstrated for the first time that 9,10-dimethyl-1,2-benzanthracene (DMBA)-treated hamsters showed hypertriglyceridemia followed by cachexia. Hypertriglyceridemia is believed to be caused in part by the decreased lipoprotein lipase (LPL) activity, and by cytokines such as tumor necrosis factor (TNF)-alpha. In addition, TNF-alpha action is associated with the LPL activity. Therefore, we determined the content of triglyceride (TG), LPL, and TNF-alpha in the serum from DMBA-treated hamsters. Elevated TG concentration in the serum of tumor-bearing hamsters was more remarkable and preceded the increase in other lipids, whereas the activity of LPL, the key enzyme of TG metabolism in vivo, was drastically reduced. TNF-alpha, known as an endogenous inhibitor of LPL activity, was detected in both the sera and the extract of tumors from DMBA-treated hamsters, whereas it was not detectable in any control samples. Pre-incubation of control sera with exogenous recombinant human TNF-alpha resulted in a potent inhibition of endogenous LPL activity in a dose-dependent manner in vitro. Therefore, the presence of TNF-alpha might lead to the increase in plasma TG mediated by LPL in tumor-bearing hamsters.
Nakajima
J
J
Department of Oral & Maxillofacial Surgery I, Matsumoto Dental College, Nagano, Japan.
Mogi
M
M
Kage
T
T
Chino
T
T
Harada
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000201:enzymology; D002610:Cheek; D006224:Cricetinae; D004195:Disease Models, Animal; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000201:enzymology / Q000209:etiology*; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000097:blood; D008297:Male; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000201:enzymology; D011994:Recombinant Proteins / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology
D002273:Carcinogens; D011994:Recombinant Proteins; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D015127:9,10-Dimethyl-1,2-benzanthracene; D008071:Lipoprotein Lipase