Effect of tumor necrosis factor (TNF) on lipid metabolism in the diabetic rat. Evidence that inhibition of adipose tissue lipoprotein lipase activity is not required for TNF-induced hyperlipidemia.

Feingold, Kenneth R.; Soued, Mounzer; Staprãns, Ilona; Gavin, Laurence A.; Donahue, M E; Huang, Bingqiao; Moser, Arthur H.; Gulli, Rocco; Grünfeld, Carl

doi:10.1172/jci113991

Cited by 119 publications

(76 citation statements)

References 29 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hyperlipidaemia produced by TNF is thought to arise as a result of the inhibition of adipose tissue lipoprotein lipase activity and has been considered important in the cachexia ( Beutler & Cerami, 1987). However, recent evidence suggests that inhibition of adipose tissue lipoprotein lipase is not required for TNF-induced hyperlipidaemia (Feingold et al, 1989) and that TNF-induced hyperlipidaemia is not inevitably linked to the syndrome of cachexia (Grunfeld et al, 1989) and this would be supported by the results of the present experiments.…”

Section: Discussionsupporting

confidence: 80%

Effect of megestrol acetate on weight loss induced by tumour necrosis factor alpha and a cachexia-inducing tumour (MAC16) in NMRI mice

Beck

Tisdale²

1990

Br J Cancer

View full text Add to dashboard Cite

Summary The effect of the synthetic progesterone, megestrol acetate, on weight loss induced by both tumour necrosis factor a (TNF) as a model for the cachexia accompanying the acquired immunodeficiency syndrome and by a cachexia-inducing tumour (MAC16) has been studied in NMRI mice. Megestrol acetate was effective in preventing weight loss in both model systems with treated animals having an increase in intake of both food and water. Megestrol acetate was unable to prevent loss of body weight in animals pair-fed with TNF treated animals, suggesting that the increase in food and water intake was responsible for the increase in body weight. Analysis of body composition showed that the major contribution to the increase in body weight in animals treated with megestrol acetate was an increase in water content, although there was also an increase in carcass fat in animals bearing the MAC16 tumour given the high dose of megestrol acetate. Animals bearing the MAC16 tumour had a significant increase in tumour weight after treatment with megestrol acetate, possibly owing to the increased plasma glucose levels. These results suggest that an increase in appetite and weight gain alone are not sufficient to justify the anticachectic effect of a particular agent and that body composition analysis and tumour growth rate are very important parameters.

show abstract

Section: Discussionsupporting

confidence: 80%

Effect of megestrol acetate on weight loss induced by tumour necrosis factor alpha and a cachexia-inducing tumour (MAC16) in NMRI mice

Beck

Tisdale²

1990

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…19 TNF does stimulate hepatic lipid synthesis in diabetic animals. 19 Fourth, TNF treatment does not decrease the clearance of triglyceriderich lipoproteins from the circulation. 111819 Finally, total hepatic trigh/ceride secretion is increased in TNFtreated animals as measured by the Triton WR-1339 technique.…”

mentioning

confidence: 95%

“…1617 In fact, LPL activity is increased in the postheparin plasma of TNF-treated animals. 16 Third, TNF is just as effective in increasing serum triglyceride levels in streptozotocin-diabetic rats in which adipose tissue LPL activity is markedly reduced secondary to diabetes 19 ; more importantly, no further decrease in adipose tissue LPL activity is seen after TNF treatment of diabetic animals. 19 TNF does stimulate hepatic lipid synthesis in diabetic animals.…”

mentioning

confidence: 99%

“…16 Third, TNF is just as effective in increasing serum triglyceride levels in streptozotocin-diabetic rats in which adipose tissue LPL activity is markedly reduced secondary to diabetes 19 ; more importantly, no further decrease in adipose tissue LPL activity is seen after TNF treatment of diabetic animals. 19 TNF does stimulate hepatic lipid synthesis in diabetic animals. 19 Fourth, TNF treatment does not decrease the clearance of triglyceriderich lipoproteins from the circulation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effect of interleukin-1 on lipid metabolism in the rat. Similarities to and differences from tumor necrosis factor.

Feingold

Soued

Adi

et al. 1991

Arterioscler Thromb

Self Cite

View full text Add to dashboard Cite

Infection and inflammation are associated with hypertriglyceridemia, which is thought to be mediated by cytokines. Previous studies at our laboratory and others have shown that tumor necrosis factor acutely increases serum triglyceride levels primarily by stimulating hepatic lipid synthesis and secretion. The role of interleukin-1 (IL-1), a cytokine that is also secreted by stimulated macrophages and that has many actions that overlap those of tumor necrosis factor, has not been studied in depth. The present study demonstrates that IL-1, at doses similar to those that cause fever and anorexia and that stimulate adrenocorticotropic hormone secretion, rapidly increases serum triglyceride levels; this elevation persists for at least 17 hours. Serum cholesterol levels are not altered by IL-1. Neither is the clearance of triglyceride-rich lipoproteins affected by IL-1. However, hepatic triglyceride secretion, measured by the Triton WR-1339 technique, is increased in IL-1-treated animals. Accompanying this stimulation in hepatic lipid secretion is an increase in de novo fatty acid synthesis in the liver. IL-1 does not increase serum free fatty acid and glycerol levels, suggesting that IL-1 does not stimulate lipolysis in vivo. Additionally, inhibition of lipolysis does not prevent the increase in serum triglyceride levels, providing further evidence that lipolysis does not play a crucial role in the increased hepatic lipid synthesis and secretion induced by IL-1. In contrast, tumor necrosis factor increases lipolysis, which contributes to the increase in serum trigtycerides. That multiple cytokines rapidly elevate plasma triglyceride levels suggest that these changes in lipid metabolism may play an important role in the organism's response to infection and inflammation. (Arteriosclerosis and Thrombosis 1991;ll:495-500)

show abstract

“…Glucose was determined using a YSI model 23A glucose autoanalyser (Yellow Springs Instruments, Yellow Springs, Ohio, USA). Plasma insulin levels were determined by radioimmunoassay, using a double antibody technique [15]. Plasma renin concentration was determined as the rate of angiotensin I generation in plasma incubated for 2 h at pH 6.5 in the presence of excess rat angiotensinogen using the method of Menard and Catt [16].…”

Section: Methodsmentioning

confidence: 99%

Effects of angiotensin II on insulin receptor binding and mRNA levels in normal and diabetic rats

et al. 1997

View full text Add to dashboard Cite

The observation that hyperinsulinaemia and insulin resistance are present in subjects with essential hypertension has led to the hypothesis that insulin is involved in the pathophysiology of this disease [1][2][3]. When considering possible pathogenetic mechanisms that could mediate the prohypertensive effect of insulin, particular attention has been paid to the renal actions of the hormone. Insulin decreases urinary sodium excretion in rats [4], dogs [5,6], and humans [7, Diabetologia (1997) Summary Both the density and level of mRNA encoding insulin receptors in the kidney are inversely related to the dietary sodium content, suggesting a feedback mechanism that limits the insulin-induced sodium retention when extracellular fluid volume is expanded. Because angiotensin II affects tissue sensitivity to insulin in humans, we investigated whether angiotensin II affects insulin receptor binding and mRNA levels in the kidney, liver, and renal arteries of normal rats and rats with streptozotocin-induced diabetes mellitus. Non-diabetic and diabetic rats were infused for 7 days with either vehicle or angiotensin II at a rate of 200 ng ⋅ kg −1 ⋅ min −1 . In a separate experiment, normal rats were treated with an angiotensin converting enzyme inhibitor (captopril, 100 mg/dl in the drinking water) or vehicle for 7 days. Regional analysis of insulin receptor binding in the kidney and renal arteries was performed by an in situ technique using computerized microdensitometry and emulsion autoradiography. Insulin receptor mRNA levels were determined in renal and hepatic tissue by Northern blot hybridization and normalized with 28S rRNA. No differences in blood pressure were observed among diabetic and non-diabetic rats infused with either vehicle or angiotensin II, whereas captopril-treated rats had significantly lower blood pressure levels than their respective controls. Angiotensin II significantly decreased plasma renin concentration in both non-diabetic and diabetic rats. Insulin receptor number was significantly greater in the renal cortex of diabetic rats than in non-diabetics, whereas no significant differences were found in the outer medulla, inner medulla, or renal arteries. Angiotensin II infusion did not affect either the number or affinity of insulin receptors in any of the renal regions studied. Insulin receptor mRNA levels were significantly greater in the kidney and liver of diabetic rats than in non-diabetics and were not affected by angiotensin II infusion. Similar to angiotensin II infusion, captopril treatment did not affect either renal insulin receptor binding or mRNA levels. Thus, diabetic rats have increased insulin receptor binding and mRNA levels in comparison to non-diabetic rats. Angiotensin II infusion and captopril treatment do not affect insulin receptor binding and mRNA levels in the kidney, arguing against a role for this peptide in the modulation of renal sensitivity to insulin. [Diabetologia (1997) 40: 770-777]

show abstract

Effect of tumor necrosis factor (TNF) on lipid metabolism in the diabetic rat. Evidence that inhibition of adipose tissue lipoprotein lipase activity is not required for TNF-induced hyperlipidemia.

Cited by 119 publications

References 29 publications

Effect of megestrol acetate on weight loss induced by tumour necrosis factor alpha and a cachexia-inducing tumour (MAC16) in NMRI mice

Effect of megestrol acetate on weight loss induced by tumour necrosis factor alpha and a cachexia-inducing tumour (MAC16) in NMRI mice

Effect of interleukin-1 on lipid metabolism in the rat. Similarities to and differences from tumor necrosis factor.

Effects of angiotensin II on insulin receptor binding and mRNA levels in normal and diabetic rats

Contact Info

Product

Resources

About