Acute metabolic effects of human recombinant tumor necrosis factor β in the rat Journal Article
| Authors: | Blumberg, D.; Tsuburaya, A.; Burt, M.; Donner, D. B.; Brennan, M. F. |
| Article Title: | Acute metabolic effects of human recombinant tumor necrosis factor β in the rat |
| Abstract: | Background: Cancer cachexia is associated with several alterations in host metabolism, including hypoaminoacidemia and an increase in gluconeogenesis (GLC) and lipolysis. Tumor necrosis factor β (TNFβ), 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 TNFβ in vivo, we examined its acute effects in the rat. Methods: Twenty-eight male Fischer rats were injected intraperitoneally with TNFβ (250 μg/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 m M alanine (ALA) or 10 m M lactate (LAC), and glucose production was measured. Rates of GLC (nmol glucose/106 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: TNFβ caused a 130% increase in gluconeogenesis from alanine (2.7±0.5 vs 1.2±0.2 nmol glucose/106 cells/min, TNF vs CTL), and a 60% increase from lactate (7.5±1.0 vs 4.6±0.5 nmol glucose/106 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. Conclusion: In vivo TNFβ causes an increase in hepatic gluconeogenesis from alanine and lactate with no change in plasma insulin or amino acids. © 1994 The Society of Surgical Oncology, Inc. |
| Keywords: | animal; metabolism; cell survival; cells, cultured; drug effect; pathology; blood; liver; cell culture; recombinant proteins; recombinant protein; rat; insulin; glucose blood level; amino acid; blood glucose; rats; amino acids; rats, inbred f344; lactic acid; lymphotoxin; gluconeogenesis; glycogen; intraperitoneal drug administration; injections, intraperitoneal; rat strain; lactates; male; article; support, u.s. gov't, p.h.s.; tumor necrosis factor β; lactic acid derivative |
| Journal Title: | Annals of Surgical Oncology |
| Volume: | 1 |
| Issue: | 5 |
| ISSN: | 1068-9265 |
| Publisher: | Springer |
| Date Published: | 1994-09-01 |
| Start Page: | 373 |
| End Page: | 377 |
| Language: | English |
| DOI: | 10.1007/bf02303808 |
| PROVIDER: | scopus |
| PUBMED: | 7850538 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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