Acute metabolic effects of human recombinant tumor necrosis factor beta in the rat.
BACKGROUND
Cancer cachexia is associated with several alterations in host metabolism, including hypoaminoacidemia and an increase in gluconeogenesis (GLC) and lipolysis. Tumor necrosis factor beta (TNF beta), a lymphokine released by mitogen-activated T lymphocytes and several cancer cell lines, causes an increase in lipolysis in 3T3L1 adipocytes. Since little is known about the metabolic effects of TNF beta in vivo, we examined its acute effects in the rat.


METHODS
Twenty-eight male Fischer rats were injected intraperitoneally with TNF beta (250 micrograms/kg) or saline (CTL), and after 4 h, isolated hepatocytes were obtained (by in situ collagenase liver perfusion [n = 12]) or aortic blood was collected (n = 16). Hepatocytes were incubated with 10 mM alanine (ALA) or 10 mM lactate (LAC), and glucose production was measured. Rates of GLC (nmol glucose/10(6) cells/min) were determined by linear regression. Plasma lactate, glucose, insulin, and amino acids (AA) (nmol/ml) were measured, and values were expressed as means +/- SEM. Comparisons between groups were made by unpaired t test or Mann-Whitney U test, and significance was defined as p < 0.05.


RESULTS
TNF beta caused a 130% increase in gluconeogenesis from alanine (2.7 +/- 0.5 vs 1.2 +/- 0.2 nmol glucose/10(6) cells/min, TNF vs CTL), and a 60% increase from lactate (7.5 +/- 1.0 vs 4.6 +/- 0.5 nmol glucose/10(6) cells/min, TNF vs CTL). Plasma insulin levels in TNF treated rats were 1.2 +/- 0.2 ng/ml compared to 1.1 +/- 0.2 ng/ml in CTL. Total amino acid levels in TNF treated rats were 3,175 +/- 111 nmol/ml compared to 3,190 +/- 103 nmol/ml in CTL.


CONCLUSIONS
In vivo TNF beta causes an increase in hepatic gluconeogenesis from alanine and lactate with no change in plasma insulin or amino acids.
Surgical Metabolism Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
D
D
Blumberg
A
A
Tsuburaya
M
M
Burt
D B
DB
Donner
M F
MF
Brennan
D000596:Amino Acids / Q000097:blood* / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000032:analysis* / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D005943:Gluconeogenesis / Q000187:drug effects*; D006003:Glycogen / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D019344:Lactic Acid; D006003:Glycogen