Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate whether interleukin 6 (IL-6) might be a potential mediator of the depleted fat reserves observed in malignancy-associated cachexia, we measured lipoprotein lipase (LPL) activity in adipose tissue of mice after administration of IL-6 or tumor necrosis factor and in cultured adipocytes after addition of these cytokines. Injection of IL-6 i.p. reduced adipose tissue LPL activity by 53% within 4.5 to 5.5 h. Injection of tumor necrosis factor elevated serum IL-6 levels and reduced adipose tissue LPL activity by 70%. Both human and murine IL-6 reduced heparin-releasable LPL activity in 3T3-L1 adipocytes in a dose-dependent manner; half-maximal inhibition of LPL activity was achieved with 5000 hybridoma growth factor units/ml. Thus, IL-6 reduces adipose LPL activity and may contribute to the loss of body fat stores associated with some cases of cancer cachexia. Since tumor necrosis factor increases circulating IL-6, some of its effects may be mediated or potentiated by IL-6.
Cancer Res 1992 Aug 01
PMID:Interleukin 6 reduces lipoprotein lipase activity in adipose tissue of mice in vivo and in 3T3-L1 adipocytes: a possible role for interleukin 6 in cancer cachexia. 163 23

Melanoma-derived lipoprotein lipase inhibitor (MLPLI) is a factor purified from the conditioned medium of a human melanoma cell line, SEKI, which induced severe cachexia in tumor-bearing nude mice. Amino acid sequencing revealed that the amino-terminal portion was identical to that of leukemia-inhibitory factor (LIF). To determine whether MLPLI is actually LIF, the expression of LIF mRNA was examined in the SEKI melanoma cell line. Northern blot analyses revealed that the cell line displayed an intense hybridizable band with a molecular size of 3.8 kilobases, suggesting that MLPLI is identical to LIF. The relationship between the development of the cancer cachexia syndrome and the expression of LIF mRNA was examined in four melanoma xenografts, SEKI, G361, A375 and MEWO, in nude mice. SEKI- and G361-bearing nude mice developed cancer cachexia syndrome, and their body weights decreased by the 25th day after the transplantation to 73.6% and 73.8% of the control, respectively. A375- and MEWO-bearing nude mice, however, did not develop the syndrome. Northern blot analyses revealed that G361 as well as SEKI expressed a large amount of LIF mRNA, but A375 and MEWO did not, suggesting a close relationship between the expression of LIF mRNA and the development of the syndrome. These data support the concept that MLPLI, or LIF, plays an important role in the development of the cancer cachexia syndrome observed in melanoma-bearing nude mice.
Cancer Res 1991 Dec 15
PMID:Cancer cachexia syndrome developed in nude mice bearing melanoma cells producing leukemia-inhibitory factor. 174 40

The growth rate of the MAC16 tumour in cachectic animals was significantly enhanced by the hypolipidemic agent bezafibrate, while the growth rate of a histologically similar tumour, the MAC13, which grows without an effect on host body compartments was unaffected. Growth of the MAC16 in vitro was unaffected by bezafibrate, suggesting that it was an in vivo phenomenon only. The stimulatory effect of bezafibrate correlated with the maximum plasma levels of free fatty acids (FFA) arising from the catabolism of adipose tissue. Accumulation of 14C-lipid from 1-14C-triolein administered by intragastric intubation was enhanced in heart, gastrocnemius muscle and tumour of bezafibrate treated animals, while the total lipid absorption did not differ from solvent treated controls. The increased lipid accumulation in the heart, but not the tumour correlated with an increased tissue lipoprotein lipase level. The increased tumour level may arise from an increased uptake of FFA arising from a weakening of the bonds between FFA and albumin. These results suggest that growth of certain tumours is dependent on maintaining sufficient lipid levels and that the lipid mobilising effect of the tumour may be necessary to sustain tumour growth.
Br J Cancer 1991 Dec
PMID:Effect of the lipid-lowering agent bezafibrate on tumour growth rate in vivo. 176 64

Impairment of the nutritional state plays a major role in the morbidity and mortality of cancer patients. However, the opportunity of providing artificial nutritional support to these patients is still debated, because of the concern that energy substrates administered to replete the host may concomitantly stimulate tumor growth. A correct nutritional approach to cancer patients should thus be based on a thorough knowledge of both host and tumor metabolic needs and host-tumor metabolic interactions. Specific modifications of plasma levels of glucogenic, aromatic, sulfur-containing and branched-chain amino acids have been demonstrated in cancer patients, indicating a specific influence of the tumor on amino acid metabolism. Little is known about protein metabolism in neoplastic tissue. Interference with tumor growth has been attempted by deprivation of single amino acids with controversial results. Increased gluconeogenesis and insulin resistance are responsible for the two main abnormalities in carbohydrate metabolism in cancer patients, namely increased glucose turnover and impaired glucose tissue disposal. Lipid metabolism is also affected by the neoplasm: soluble factors such as "lipid-mobilizing factor" lead to increased fat mobilization from adipose tissue; plasma elimination of exogenous triglycerides has also been found to be reduced probably because of a tumor-related decrease in lipoprotein lipase activity. The differences in glucose and fat utilization between tumor and host should be considered in the nutritional approach to cancer patients. Data in this respect are controversial and have been obtained only in experimental animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal substrate metabolism and nutritional strategies in cancer management. 176 60

To elucidate the mechanisms of hypertriglyceridemia observed in the tumor-bearing rat, tissue lipoprotein lipase (LPL) activity and LPL mRNA levels were examined in the fed and fasted states at different degrees of tumor burden and after tumor removal. LPL activity in the epididymal fat pad and cardiac muscle in the 24-h-fasted rats was significantly decreased with increasing tumor burden (r = -0.53, P less than 0.05 and r = -0.72, P less than 0.01, respectively). Tumor removal completely reversed these changes. In contrast, no change in LPL activity was detected in the fed state since food intake stimulated LPL activity to the same extent in both tumor-bearing (TBR) and control rats. LPL activity in the diaphragm and skeletal muscle was only marginally altered in TBR, as compared to controls. LPL mRNA from the epididymal fat pad and cardiac muscle migrated to the same site on agarose gel and hybridized to a LPL-specific complementary DNA probe. The decline in LPL activity in epididymal fat pad observed in TBR was associated with a decrease in LPL mRNA levels. In contrast, there was no significant difference in LPL mRNA levels in cardiac muscle between the two groups despite significantly suppressed enzyme activity in tumor bearers. This study provides evidence that hypertriglyceridemia in TBR is due in part to tumor-dependent suppression of adipose and cardiac LPL activity in the fasted state, which is stimulated by the presence of tumor. Unlike cardiac LPL, the tumor-induced changes in adipose LPL activity are regulated at the mRNA level in this tumor model.
Cancer Res 1991 Feb 01
PMID:Tumor-induced alterations in tissue lipoprotein lipase activity and mRNA levels. 198 26

The effect of weight loss during cancer cachexia on the plasma levels of free fatty acids (FFA) and triglycerides, and on the tissue levels of lipoprotein lipase (LPL), has been studied in mice bearing an experimental colon adenocarcinoma (MAC16). Despite extensive mobilisation of host body fat reserves, plasma levels of triglycerides were reduced irrespective of the extent of weight loss. The plasma levels of FFA also showed an initial decrease with weight loss, followed by a rise peaking at a weight loss of about 2 g, and thereafter the levels decreased with increasing weight loss. The level of LPL in both heart and adipose tissue showed an initial rise with increasing weight loss also peaking at a weight loss of approximately 2.5 g, followed by a decrease with further weight loss. The increased LPL would provide an increased level of fatty acids for oxidation in the cachectic state and would account for the effect on plasma FFAs and triglycerides.
Cancer Lett 1991 Apr
PMID:Changes in activity of lipoprotein lipase, plasma free fatty acids and triglycerides with weight loss in a cachexia model. 202 78

Abnormalities in lipid metabolism have been widely described in cancer-bearing patients and animals. In particular, the presence of the tumor seems to profoundly affect triglyceride (TG) utilization by interfering with lipoprotein lipase (LPL) activity. Exogenous TG plasma clearance was evaluated in 10 nonmalnourished patients with cancers of various origin and 10 normolipidemic volunteers by means of a three-stage intravenous lipid clearance test. This technique allows precise determination of both the fractional removal rate (K2) and the maximal clearing capacity (K1) for exogenous lipids. Mean K2 values (min-1) were found to be significantly reduced in cancer patients compared with control subjects (0.07 +/- 0.006 vs 0.13 +/- 0.013 SEM, p less than 0.005). K1 values (mumol/L/min) were also found to be significantly lower in cancer patients than in the control group (109.43 +/- 6.3 vs 143 +/- 6.3 SEM, p less than 0.01). The data obtained indicate that the capacity to eliminate exogenous lipids from the bloodstream is reduced in cancer-bearing patients. This may be the consequence of a tumor-related impairment of LPL system activity.
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PMID:Plasma clearance of exogenous lipids in patients with malignant disease. 213 27

Cachectin/tumor necrosis factor (TNF-alpha) is a macrophage-secreted cytokine initially found to be a lipoprotein lipase-suppressing serum factor in cachectic, parasite-infected animals. Cloning of the cDNA encoding the gene for cachectin enabled biosynthesis of recombinant human cachectin and proof that the protein is identical to TNF-alpha. Numerous biological activities have subsequently been attributed to this pluripotent cytokine. In addition to suppressing LPL, cachectin/TNF mediates decreased lipogenic enzyme synthesis in adipocytes, causing a state of "cellular cachexia" in vitro. Similarly, catabolic cellular energy responses are induced by cachectin/TNF in cultured skeletal muscle cells which exhibit accelerated glycogenolysis, enhanced lactate production, and increased expression of hexose transporters. Persistent cachectin/TNF production occurs in chronic infection and malignancy, and chronic exposure induces a cachexia syndrome characterized by anorexia, weight loss, and anemia. Acute systemic appearance of cachectin/TNF is capable of inducing a state of lethal shock, disseminated hemorrhagic necrosis, catabolic hormone release, and multiple organ injury. Inhibiting the toxic effects of cachectin/TNF with monoclonal anti-cachectin antibodies during overwhelming Gram-negative bacteremia confers protection against septic shock. In these studies, the unprotected controls succumbed within hours, but baboons immunized against cachectin/TNF did not develop the characteristic increases of IL-1, IL-6, or catabolic stress hormones and did not die, suggesting that cachectin/TNF is a pivotal, proximal factor in the humoral cascade mediating septic shock syndrome. Recent evidence indicates that when produced in lesser quantities, cachectin/TNF may participate in the degradative and reparative mechanisms of physiological tissue remodelling and homeostasis. Future studies of the immunological and metabolic effects of cachectin/TNF should lead to a better understanding of the pathogenesis of infection and inflammation.
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PMID:Metabolic responses to cachectin/TNF. A brief review. 219 78

The effect of a variety of cytokines on lipid metabolism in 3T3 L1 mouse fibroblasts and adipocytes was studied. Uptake of [3H]acetate by adipocytes and heparin-releasable lipoprotein lipase activity was inhibited after treatments of the cells with picomolar concentrations of recombinant human tumor necrosis factor alpha (rHuTNF-alpha), human tumor necrosis factor beta (rHuTNF-beta, also called lymphotoxin), murine interferon-gamma (rMuIFN-gamma), and a human hybrid interferon-alpha [rHuIFN-alpha 2/alpha 1 (Bgl II)]. Recombinant human interferon-gamma (rHuIFN-gamma), natural human colony-stimulating factor (HuCSF), and human interleukin 2 (HuIL-2) had no effect. Similar though less-marked suppression of [3H]acetate uptake by cytokines was seen in 3T3 L1 fibroblasts. Cytokines inhibited the incorporation of [3H]acetate into both membrane and storage lipids in the adipocytes. In addition to blocking lipid uptake and synthesis, rHuTNF-alpha and -beta, and rMuIFN-gamma stimulated the release of free fatty acid into the medium from adipocytes. Binding studies suggest that rHuTNF-alpha and rHuTNF-beta compete for the same cell-surface receptor on 3T3 L1 adipocytes, while rMuIFN-gamma binds to a separate receptor. The binding of rTNF-alpha to both adipocytes and fibroblasts can be significantly enhanced by preexposure of the cells to rMuIFN-gamma. There appear to be both high- and low-affinity receptors for rHuTNF-alpha on adipocytes, whereas fibroblasts exhibit a single class of high-affinity receptors. These results suggest that a variety of structurally distinct cytokines possess lipid mobilization activity, which may be of critical importance to the host in defense against infection or malignancy.
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PMID:Interferons and tumor necrosis factors have similar catabolic effects on 3T3 L1 cells. 243 Feb 84

The effects of the cytokine cachectin/tumor necrosis factor (TNF) on human adipose tissue lipoprotein lipase (LPL) were studied. TNF is produced by activated macrophages and is thought to play a role in mediating hypertriglyceridemia and wasting of adipose tissue triglyceride stores (cachexia) that often accompany infection and malignancy. TNF effects were studied in human adipose tissue fragments maintained in organ culture in the presence of insulin and dexamethasone to induce high LPL activity. Addition of TNF to the culture medium for 20 h caused a dose-dependent inhibition of LPL activity to an average of 37% of controls at 50 U/ml TNF. This inhibition of LPL activity was explained by specific decreases in levels of LPL mRNA (to 40% of controls) and rates of LPL synthesis determined by biosynthetic labeling and immunoprecipitation (to 32% of controls). The decline in LPL synthesis was specific, as it occurred despite a small increase in overall protein synthesis in the presence of TNF. Comparable decreases in LPL activity were observed when TNF was added to adipose tissue cultured solely in the presence of insulin. Thus, similar to results in rodent models, TNF is a potent inhibitor of LPL gene expression in human adipose tissue. TNF may therefore play a role in the disorders of triglyceride catabolism and the pathogenesis of cachexia that occur with stimulation of the immune system in humans.
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PMID:Cachectin/tumor necrosis factor decreases human adipose tissue lipoprotein lipase mRNA levels, synthesis, and activity. 269 92


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