scholarly journals Pharmacological interference with tissue hypercatabolism in tumour-bearing rats

1994 ◽  
Vol 299 (1) ◽  
pp. 71-78 ◽  
Author(s):  
L Tessitore ◽  
P Costelli ◽  
F M Baccino
Keyword(s):  
Adipose Tissue ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Muscle Protein ◽  
Plasma Corticosterone ◽  
High Plasma ◽  
Liver Protein ◽  
Tissue Mass ◽  
Anabolic Hormone ◽  
Necrosis Factor

Marked loss of body weight and profound waste of both skeletal muscle and white adipose tissue occur in rats into which the ascites hepatoma Yoshida AH-130 has been transplanted, associated with marked perturbations in the hormonal homoeostasis and the presence of circulating tumour necrosis factor and high plasma levels of prostaglandin E2 [Tessitore, Costelli and Baccino (1993) Br. J. Cancer 67, 15-23]. On the basis of previous findings, the present study examined whether the development of cachexia in this model system could be significantly affected by adrenalectomy or by pharmacological treatments that may interfere with proximal or distal mediators of tissue hypercatabolism. In no instance was tumour growth modified. Medroxyprogesterone acetate, an anabolic-hormone-like drug, was completely ineffective. In adrenalectomized animals, although changes such as the elevation of plasma triacylglycerols and corticosterone were corrected, the general course of cachexia was not modified. A partial prevention of muscle waste was observed with acetylsalicylic acid, a non-steroidal anti-inflammatory drug, or with leupeptin, a proteinase inhibitor. Insulin afforded the most significant preservation of muscle protein and adipose-tissue mass, which were maintained close to control values even 10 days after transplantation. The effects of insulin on gastrocnemius muscle and liver protein content were exerted by slowing down protein turnover, mainly enhancing synthesis. Consistently, the total free amino acid concentration in the gastrocnemius of insulin-treated rats 10 days after tumour transplantation was close to that of controls. Although treatment with insulin decreased plasma corticosterone to normal values, it did not modify the circulating level of tumour necrosis factor. On the whole these data show that it seems possible to prevent, at least in part, the tissue waste that characterizes cancer cachexia by purely pharmacological means.

scholarly journals Tumour necrosis factor alpha: a key regulator of adipose tissue mass

2003 ◽  
Vol 177 (3) ◽  
pp. 351-355 ◽  
Author(s):  
JP Warne
Keyword(s):  
Adipose Tissue ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Alpha ◽  
Tissue Mass ◽  
Necrosis Factor Alpha ◽  
General Role ◽  
Adipose Tissue Mass ◽  
Factor Alpha ◽  
Necrosis Factor

In addition to its established role in the immune system, tumour necrosis factor alpha (TNFalpha) exerts complex regulatory actions on adipose tissue. TNFalpha is produced in and secreted by the adipocyte and thus is in a position to exert a paracrine and/or autocrine role within adipose tissue. TNFalpha affects many aspects of adipocyte function, from adipocyte development to lipid metabolism. Bringing together all of these diverse actions, TNFalpha appears to play a general role in reducing adipose tissue mass. Dysregulation of TNFalpha production and/or action could be one facet in the development of cachexia and obesity, as well as associated metabolic disorders such as insulin resistance.

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.

Cardiac Muscle Protein Gene Expression in the Endotoxin-Treated Rat

1994 ◽  
Vol 87 (5) ◽  
pp. 539-546 ◽  
Author(s):  
D. C. Macallan ◽  
G. E. Griffin
Keyword(s):  
Cardiac Muscle ◽  
Myosin Heavy Chain ◽  
Tumour Necrosis Factor ◽  
Heavy Chain ◽  
Tumour Necrosis ◽  
Muscle Protein ◽  
Mrna Levels ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

1. Sepsis is associated with marked changes in cardiac muscle protein synthesis. Such changes may be the result of altered transcription of specific myofibrillar protein mRNAs. 2. In order to investigate myofibrillar protein gene expression, a rat model of sepsis was used. Adult rats were given a single sub-lethal dose of lipopolysaccharide by the intraperitoneal route. At various times thereafter, rats were killed and ventricular muscle was removed. RNA was extracted and transferred to nylon membranes. Changes in expression of mRNA for α- and β-myosin heavy chain, α-actin, cardiac troponin C and carbonic anhydrase III were detected by Northern hybridization. 3. After treatment with lipopolysaccharide, mRNA for β-myosin heavy chain increased to 260% of control values at 24 h and reached a maximum of 310% at 48 h. α-Myosin heavy chain mRNA levels fell to 72% of control values at 24 h. mRNA levels for α-actin, cardiac troponin C and carbonic anhydrase III remained unchanged. 4. In order to investigate the role of tumour necrosis factor-α in this process, some rats were pretreated with monoclonal antibody against tumour necrosis factor-α before receiving lipopolysaccharide. Such animals showed an absence of tumour necrosis factor-α bioactivity in plasma, but changes in myocardial protein mRNA levels were no different from those seen in animals receiving lipopolysaccharide alone. 5. The reduction in protein synthesis in cardiac muscle in sepsis does not appear to be the result of reduced expression of genes for structural or soluble muscle protein. Rather there is a paradoxical increase in β-myosin heavy chain expression, which may represent a protective mechanism. Tumour necrosis factor-α does not appear to be involved in the mediation of these changes.

scholarly journals Dietary fat modifies some metabolic actions of human recombinant tumour necrosis factor α in rats

1990 ◽  
Vol 63 (3) ◽  
pp. 653-668 ◽  
Author(s):  
D. C. Bibby ◽  
R. F. Grimble
Keyword(s):  
Tumour Necrosis Factor ◽  
Rectal Temperature ◽  
Tumour Necrosis ◽  
Coconut Oil ◽  
Liver Protein ◽  
Tumour Necrosis Factor Α ◽  
Zn Content ◽  
Factor Α ◽  
Necrosis Factor ◽  
Maize Oil

To examine how fat might influence the metabolic effects of tumour necrosis factor α (TNFα), human recombinant TNFα was given intravenously to rats that had been fed for 12 weeks on diets containing (g/kg) 200 maize oil or 190 coconut oil+10 maize oil. Rectal temperature and tissue composition measurements were made 8 and 24 h after injection. Ambient temperatures of 20° and 25° were employed to accentuate rectal temperature changes. Doses of 30 and 300 μg TNFα/kg body-weight were given, and brought about depression of serum zinc and albumin and elevation of copper. Muscle protein content was decreased and liver protein and Zn content enhanced by TNFα. Serum Zn and liver Zn content were negatively correlated 8 h after injections. Hypothermia developed within 1 h of injection. All responses except the rise in serum Cu and gain in liver Zn were more intense at the higher than at the lower dose of TNFα. Hypothermia was exacerbated by an environmental temperature of 20°. The coconut-oil diet blunted the hypothermia and likewise the changes in serum albumin and Cu content 8 h after injections and in muscle and liver protein after 24 h. Changes in eicosanoid metabolism may be involved in the modulatory effects of the coconut-oil-enriched diet.

scholarly journals Downregulation of zinc-α2-glycoprotein in adipose tissue and liver of obese ob/ob mice and by tumour necrosis factor-α in adipocytes

2009 ◽  
Vol 204 (2) ◽  
pp. 165-172 ◽  
Author(s):  
T Mracek ◽  
D Gao ◽  
T Tzanavari ◽  
Y Bao ◽  
X Xiao ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Content ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Zucker Rats ◽  
Potential Candidate ◽  
Mrna Levels ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Zinc-α2-glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested as a potential candidate in the modulation of body weight. We investigated the effect of increased adiposity on ZAG expression in adipose tissue and the liver and on plasma levels in obese (ob/ob) mice compared with lean siblings. The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-α (TNFα) on ZAG expression in adipocytes. Zag mRNA levels were significantly reduced in subcutaneous (fourfold) and epididymal (eightfold) fat of ob/ob mice. Consistently, ZAG protein content was decreased in both fat depots of ob/ob mice. In the liver of obese animals, steatosis was accompanied by the fall of both Zag mRNA (twofold) and ZAG protein content (2.5-fold). Plasma ZAG levels were also decreased in obese mice. In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese (fa/fa) Zucker rats. In contrast to Zag expression, Tnfα mRNA levels were elevated in adipose tissue (twofold) and the liver (2.5-fold) of ob/ob mice. Treatment with TNFα reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFα treatment. It is concluded that ZAG synthesis in adipose tissue and the liver is downregulated, as are its circulating levels, in ob/ob mice. The reduced ZAG production may advance the susceptibility to lipid accumulation in these tissues in obesity, and this could be at least in part attributable to the inhibitory effect of TNFα.

scholarly journals Tumour necrosis factor-α (TNF-α) polymorphisms -857C/A and -863C/A are associated with TNF-α secretion from human adipose tissue

Diabetologia ◽  
2001 ◽  
Vol 44 (5) ◽  
pp. 654-655 ◽  
Author(s):  
T. Skoog ◽  
P. Eriksson ◽  
J. Hoffstedt ◽  
M. Rydén ◽  
A. Hamsten ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Human Adipose Tissue ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor
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