scholarly journals Regulation of lipoprotein lipase synthesis in 3T3-L1 adipocytes by cachectin Further proof for identity with tumour necrosis factor

1986 ◽  
Vol 240 (2) ◽  
pp. 601-604 ◽  
Author(s):  
S R Price ◽  
T Olivecrona ◽  
P H Pekala
Keyword(s):  
Protein Synthesis ◽  
Conditioned Medium ◽  
Tumour Necrosis Factor ◽  
Lipoprotein Lipase ◽  
Tumour Necrosis ◽  
Secretory Protein ◽  
Necrosis Factor ◽  
Precipitable Protein

We investigated the mechanism by which the endotoxin-induced macrophage secretory protein cachectin is able to suppress the activity of lipoprotein lipase in 3T3-L1 adipocytes. The loss in activity results from an effect on the synthesis of the enzyme, as determined by a decreased incorporation of [35S]methionine into immunoprecipitable lipoprotein lipase. The results were nearly identical whether crude conditioned medium or a highly purified preparation was utilized as a source of cachectin. [35S]Methionine incorporation into acid-precipitable protein was minimally affected by purified cachectin, suggesting that the suppression of the lipoprotein lipase was not due to a general suppression of protein synthesis. These results, taken together with our previous work, provide additional evidence that cachectin and tumour necrosis factor are functionally identical.

Influence of butter and of corn, coconut and fish oils on the effects of recombinant human tumour necrosis factor-α in rats

1993 ◽  
Vol 84 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Hilda M. Mulrooney ◽  
Robert F. Grimble
Keyword(s):  
Protein Synthesis ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Coconut Oil ◽  
Complement C3 ◽  
Tumour Necrosis Factor Α ◽  
Zinc Concentrations ◽  
Factor Α ◽  
Lung And Kidney ◽  
Necrosis Factor

1. Tumour necrosis factor-α is produced in response to inflammatory stimuli. Fish oil can suppress the production and actions of cytokines. Little information is available on the effects of other fats on cytokine biology. We compared the effects of fats, with a wide range of fatty acid characteristics, on the effects of tumour necrosis factor-α on protein and zinc metabolism in rats. 2. Weanling rats were fed for 8 weeks on diets containing 10% fat in the form of corn, fish or coconut oils or butter before an intraperitoneal injection of recombinant human tumour necrosis factor-α was given. Measurements were made 24 h after the injection. 3. In rats fed corn oil, food intake was reduced by 62% and rates of protein synthesis were increased by 86, 32 and 39% in the liver, lung and kidney, respectively. Zinc concentrations increased by 23% in the liver but decreased by 10% in the kidney. Plasma caeruloplasmin and complement C3 levels increased by 25% and 28%, respectively, and plasma albumin level decreased by 24%. 4. Fish oil prevented the increase in hepatic protein synthesis and changed the response of protein synthesis in lung and kidney to a decrease. Changes in hepatic and renal zinc concentrations were prevented. The response of the plasma caeruloplasmin level was unaltered but those of the plasma complement C3 and albumin concentrations were prevented. 5. Coconut oil and butter, although similarly low in linoleic acid, differed in their modulatory effects. With the exception of the rise in the plasma complement C3 concentration, all responses were prevented or greatly inhibited in rats fed butter. In rats fed coconut oil the increase in liver protein synthesis was reduced but that in the lung and kidney was unaffected. Changes in hepatic zinc concentration were unaffected but those in renal zinc concentration were prevented. 6. Fish and coconut oils and butter reduced the intensity of anorexia caused by tumour necrosis factor-α. The extent to which fats rich in (n-3) polyunsaturates or poor in linoleic acid modulate the metabolic response to tumour necrosis factor-α depends upon additional fatty acid characteristics.

scholarly journals Increased intestinal protein synthesis during sepsis and following the administration of tumour necrosis factor α or interleukin-1 α

1992 ◽  
Vol 286 (2) ◽  
pp. 585-589 ◽  
Author(s):  
D von Allmen ◽  
P O Hasselgren ◽  
T Higashiguchi ◽  
J Frederick ◽  
O Zamir ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Interleukin 1 ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Jejunal Mucosa ◽  
Ileal Mucosa ◽  
Intestinal Protein ◽  
Necrosis Factor

The influence of sepsis on intestinal protein synthesis was studied in rats. Sepsis was induced by caecal ligation and puncture (CLP); control rats were sham-operated. Protein synthesis was measured in vivo in the jejunum and ileum following a flooding dose of [14C]leucine. At 8 h after CLP the protein synthesis rate was increased by approx. 15% in jejunal mucosa, and at 16 h after CLP, the protein synthesis rate was increased by 50-60% in the mucosa and seromuscular layer of both jejunum and ileum. In a second series of experiments, rats were treated with recombinant tumour necrosis factor alpha (rTNF alpha) or recombinant interleukin-1 alpha (rIL-1 alpha) administered at a total dose of 300 micrograms/kg body weight over 16 h. Control rats received corresponding volumes of solvent. Treatment with rTNF alpha resulted in an approx. 25% increase in mucosal protein synthesis in jejunum. Following treatment with rIL-1 alpha, protein synthesis increased by 25% in jejunal mucosa and almost doubled in ileal mucosa. The results suggest that sepsis stimulates intestinal protein synthesis and that this response may, at least in part, be mediated by TNF and/or IL-1.

scholarly journals Regulation of lipoprotein lipase mRNA content in 3T3-L1 cells by tumour necrosis factor

1988 ◽  
Vol 249 (3) ◽  
pp. 765-769 ◽  
Author(s):  
P Cornelius ◽  
S Enerback ◽  
G Bjursell ◽  
T Olivecrona ◽  
P H Pekala
Keyword(s):  
Tumour Necrosis Factor ◽  
Lipoprotein Lipase ◽  
Tumour Necrosis ◽  
Time Course ◽  
Northern Blot Analysis ◽  
Cdna Probe ◽  
Mrna Content ◽  
Normal Increase ◽  
Delayed Time ◽  
Necrosis Factor

Tumour necrosis factor (TNF) was previously shown to suppress lipoprotein lipase (LPL) synthesis and activity in 3T3-L1 adipocytes. The present study examined the effect of TNF on amounts of mRNA for LPL in 3T3-L1 cells. Northern-blot analysis of polyadenylated RNA using a cDNA probe to guinea-pig LPL identified two predominant species of LPL message, 3.7 and 3.9 kilobases in size. The steady-state amounts of these mRNAs increased 10-fold upon expression of the adipocyte phenotype. A single dose of 1.5 nM-TNF decreased LPL mRNA by approx. 60% in 17 h with a corresponding decrease in LPL activity, an effect that was reversed 48 h after exposure to TNF. The results demonstrate that TNF reversibly down-regulates LPL mRNA in fully differentiated 3T3-L1 adipocytes. Cells induced to differentiate in the presence of 1.5 nM-TNF exhibited a delayed time course for development of the adipocyte phenotype, as judged by attenuation of the normal increase in LPL mRNA that occurs with differentiation.

scholarly journals Interferon-α induces sensitization of cells to inhibition of protein synthesis by tumour necrosis factor-related apoptosis-inducing ligand

FEBS Journal ◽  
2006 ◽  
Vol 273 (16) ◽  
pp. 3698-3708 ◽  
Author(s):  
Ian W. Jeffrey ◽  
Androulla Elia ◽  
Stephanie Bornes ◽  
Vivienne J. Tilleray ◽  
Karthiga Gengatharan ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Interferon Α ◽  
Inhibition Of Protein Synthesis ◽  
Necrosis Factor

scholarly journals Regulation of lipoprotein lipase activity and mRNA content in rat epididymal adipose tissue in vitro by recombinant tumour necrosis factor

1990 ◽  
Vol 269 (1) ◽  
pp. 123-126 ◽  
Author(s):  
A G Mackay ◽  
J D Oliver ◽  
M P Rogers
Keyword(s):  
Adipose Tissue ◽  
Tumour Necrosis Factor ◽  
Lipoprotein Lipase ◽  
Tumour Necrosis ◽  
Epididymal Adipose Tissue ◽  
Mrna Levels ◽  
Isolated Adipocytes ◽  
Necrosis Factor

Tumour necrosis factor (TNF) has previously been shown to decrease lipoprotein lipase (LPL) activity and mRNA levels in 3T3-L1 cells and in adipose tissue from rats and guinea pigs when injected in vivo, but not to alter LPL activity in human adipocytes incubated in vitro. The effect of recombinant human TNF on LPL activity and mRNA levels in rat epididymal adipose tissue incubated in vitro was examined. LPL activity and mRNA levels fell in adipose tissue taken from fed rats and incubated in Krebs-Henseleit bicarbonate medium with glucose. The addition of insulin and dexamethasone prevented these falls. TNF (400 ng/ml) produced a fall of approx. 50% in LPL activity after 2 h of incubation and of approx. 30% in LPL mRNA levels after 3 h. TNF did not decrease LPL activity in isolated adipocytes. These results demonstrate that rat adipose tissue incubated in vitro is responsive to TNF whereas isolated adipocytes are not.

Anti-Tumour Necrosis Factor-α Treatment Interferes with Changes in Lipid Metabolism in a Tumour Cachexia Model

1994 ◽  
Vol 87 (3) ◽  
pp. 349-355 ◽  
Author(s):  
Neus Carbó ◽  
Paola Costelli ◽  
Luciana Tessitore ◽  
Gregory J. Bagby ◽  
Francisco J. López-Soriano ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Tumour Necrosis Factor ◽  
Lipoprotein Lipase ◽  
Lipase Activity ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Lipoprotein Lipase Activity ◽  
Tumour Bearing ◽  
Factor Α ◽  
Necrosis Factor

1. Rats bearing the Yoshida ascites hepatoma AH-130 showed an important decrease in white adipose tissue lipoprotein lipase activity as compared with non-tumour bearing rats. This was associated with a lower adipose tissue mass, as estimated from the weight of the lumbar fat-pads. Conversely, lipoprotein lipase activity was markedly increased in brown adipose tissue and heart. 2. These changes were associated with a distinct hyperlipaemia, essentially manifested as an increase in circulating triacylglycerol levels, whereas no changes were observed in glycaemia. 3. Tumour-bearing rats were treated with a polyclonal anti-murine tumour necrosis factor-α antibody or with a non-immune IgG preparation. Control animals were either untreated or received a nonimmune IgG preparation. Anti-tumour necrosis factor-α treatment resulted in a significant increase in lipoprotein lipase activity in white adipose tissue in animals bearing a tumour growing exponentially (day 4 after inoculation) as compared with the animals receiving a non-immune goat IgG preparation. In addition, animals bearing an stationary tumour (day 7 after inoculation) and submitted to anti-tumour necrosis factor-α treatment had a higher adipose tissue lipoprotein lipase activity as compared with the IgG- or the non-treated groups. Correspondingly, circulating triacylglycerol levels were markedly decreased, with a lower hyperlipaemia than in control tumour-bearing rats. 4. These observations suggest that tumour necrosis factor-α is involved in activating the lipid metabolic changes that develop in rats after transplantation of a fast-growing tumour.

scholarly journals Effect of recombinant human tumour necrosis factor α on protein synthesis in liver, skeletal muscle and skin of rats

1989 ◽  
Vol 258 (2) ◽  
pp. 493-497 ◽  
Author(s):  
Y Charters ◽  
R F Grimble
Keyword(s):  
Protein Synthesis ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Muscle Protein ◽  
Liver Protein ◽  
Post Injection ◽  
Synthetic Rate ◽  
Rna Content ◽  
Tibialis Muscle ◽  
Necrosis Factor

Bacterial endotoxins cause enhanced protein metabolism in liver, and protein catabolism in muscle and skin. These effects may be mediated by cytokines such as interleukin 1 (IL1) and tumour necrosis factor (TNF). The study investigates the timing and magnitude of effects of recombinant human TNF alpha on protein synthesis and protein and RNA content of the liver, tibialis muscle and skin of Wistar rats. Intravenous doses of 30 and 300 micrograms/kg of body weight were used and effects examined 8 h and 24 h after injection. Muscle protein content and synthetic rate were reduced at 8 h post-injection by over 18% and 20% respectively. Protein synthesis returned to normal after the lowest dose but remained depressed 24 h after the highest dose due to the accompanying anorexia. Opposite effects were observed in liver. Protein fractional synthetic rate (FSR) was increased by over 26% at 8 h post-injection and remained elevated 24 h after the higher but not lower dose of TNF. Total protein and RNA contents were significantly higher than controls at this time. Skin protein synthesis was unaffected by TNF; however an increase in protein and RNA content was observed at 8 h post-injection with the lower dose of TNF. Liver and muscle respond in a similar but more rapid way to TNF than to endotoxin. The response of skin is however totally different. While muscle may contribute amino acids for enhanced hepatic protein synthesis following exposure to TNF, skin does not.

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