Perturbations of triglycerides but not of cholesterol metabolism are prevented by anti-tumour necrosis factor treatment in rats bearing an ascites hepatoma (Yoshida AH-130)

Abstract

In the past few years a large body of evidence has been accumulated indicating a possible central role of choksterol in the pathobiology of cancer. Alterations in the synthesis, uptake and intracellular content of cholesterol have been observed in a variety of experimental tumour models as well as in different types of human neoplasms (Anderson et al., 1981;Coleman and Lavietes, 1981;Yachnin et al., 1983;Dessi et al., ,b, 1994.Choksterol perturbations also include change in lipoprotein profiles in plasma compartment. In particular, a definite decrease in high-density lipoprotein (HDL) klvels is a consistent finding in both experimental rat tumours and human neoplass (Dessi et at., 1991(Dessi et at., ,b, 1994 despite the differences reported to exist between lipoprotein metabolism in rodents and humans (Dietschy et al., 1993). In contrast, changes in other serm lipid parameters, such as total cholsterol and tnglyceride klvels, appear to vary and to be speces specific and dependent on the histological type or tumour grade (Dessi et al., 1991(Dessi et al., ,b, 1994. Therefore, it is possible that the mechanistic basis for the altered HDL levels is different from that responsible for the observed changes in other serum lipid parameters. Admittedly, HDLs play an important role in the transport of excess cholesterol from extrahepatic tisues to the liver for reutilisation or excretion into bile (reverse cholesterol transport). It is thus conceivable that the observed low levels of HDL-cholesterol may be related, at least in part, to a decrased choklsterol efflux to HDL as a consequence of increased utilisation and storage in actively proliferating tissues, such as neoplasms. However, since precursor prticles of HDL are thought to derive from lipolysis of triglyceride rich lipoproteins (Eisenberg, 1984) (Eisnberg, 1984), the possibility that low HDL cholesterol concentrations observed during tumour growth may be secondary to the decreased triglyceride clarance from plasna, as a result of LPL inhibition, must also be considered Tumour necrosis factor (rNF), a pleiotropic cytokine primarily produced by activated macrophages in response to invasve stimuli (Beutler and Cerami, 1988), has been frequently reported as beng responsible for changes in lipid metaboism which occur in association with infections and tumours in a wide variety of species, including humans and rats (Feingold et al., 1987(Feingold et al., , 1992 Harada et al., 1990). TNF might affect plasm cholesterol, triglyceride and lipoprotein levels by both inhibition of adipose LPL activity and/or stimulation of hepatic lipogenesis (Feingold et al., 1992(Feingold et al., , 1993 lipid metabolism in rats bearing ascites hepatoma Yoshida AH-130 has been previously investigated in our laboratories. This tumour causes in the host a rapid loss of body weight, associated with mared perturbations of both protein (Tessitore et al., 1987 and lipid metabolism . Increased synthesis and progressive accumulation of cholesterol were observed in AH-130 cells. During tumour gr...

Mechanisms to explain wasting of muscle and fat in cancer cachexia

“…Cholesterol perturbations during cancer include changes in lipoprotein profiles, in particular an important decrease in the amount of cholesterol transported in the highdensity lipoproteins (HDL) fraction. This finding has been observed in both experimental animals and human subjects [73][74][75]. HDL plays an important role in the transport of excess cholesterol from extrahepatic tissues to the liver for reutilization or excretion into bile (reverse cholesterol transport).…”

“…Hypercholesterolaemia is often seen in both tumourbearing animals and humans with cancer [73][74][75]. Interestingly, most cancer cells show an altered regulation in cholesterol biosynthesis showing a lack of feedback control on 3-hydroxy-3-methylglutaryl CoA reductase, the key enzyme in the regulation of cholesterol biosynthesis.…”

Effect of oral administration of ethanolic root extract of Tinospora cordifolia on aflatoxin B1-induced toxicity in swiss albino mice

“…[63] Deregulated cholesterogenesis observed in tumors, implicated an over-production, and could result in enrichment of the tumor cell membrane with cholesterol. This may be capable of inducing the cell population into greatly enhanced proliferative activity.…”

Retracted: Metabolic parameters in psoriatic patients treated with interleukin‐12/23 blockade (ustekinumab)

“…Also, low levels of IL‐10 in psoriatic patients were linked to metabolic syndrome, weight gain and insulin resistance . One would expect an antagonist to these pro‐inflammatory cytokines to have an opposite effect, however, studies have reported increased levels of triglycerides in mice treated with anti TNF‐α . Significant weight gain and increased BMI was also reported after anti‐TNF‐α treatment .…”