Uptake and metabolism of free fatty acids by the morris 7777 hepatoma and host rat liver

Morton, Richard E.; Waite, Moseley; King, Virginia L.; Morris, Harold P.

doi:10.1007/bf02535380

Cited by 6 publications

(3 citation statements)

References 19 publications

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“…This accumulation may be helpful in the management of liver metastasis. Subcutaneously transplanted tumours proliferate more rapidly than their blood supply (Morton et al, 1982). This may partially explain the slower decay of radioactivity in tumour tissue relative to the liver within the 96-h period of the present experiment, although this explanation cannot account for the similar slow decay in brain and testes/ovaries, which may be related to the high lipid contents of these organs.…”

Section: Discussionmentioning

confidence: 57%

“…It has been proposed elsewhere (Voss and Sprecher, 1988) that AA produced in liver can be transported and used for membrane synthesis in cells and tissues that do not have an adequate capacity to make sufficient AA from n-6 fatty acid precursors. However, it is likely that the altered radiolabelled fatty acid composition mirrors changes in the metabolic pathways of the tumours (DeTomas and Mercuri, 1977;Morton et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

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In vivo and in vitro biotransformation of the lithium salt of gamma-linolenic acid by three human carcinomas

Antueno¹,

Elliot²,

Ells³

et al. 1997

Br J Cancer

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Summary Lipid metabolism has been considered recently as a novel target for cancer therapy. In this field, lithium gamma-linolenate (LiGLA) is a promising experimental compound for use in the treatment of human tumours. In. vivo and in vitro studies allowed us to assess the metabolism of radiolabelled LiGLA by tumour tissue and different organs of the host. In vitro studies demonstrated that human pancreatic (AsPC-1), prostatic (PC-3) and mammary carcinoma (ZR-75-1) cells were capable of elongating GLA from LiGLA to dihomo-gamma-linolenic acid (DGLA) and further desaturating it to arachidonic acid (AA). AsPC-1 cells showed the lowest A5-desaturase activity on DGLA. In the in vivo studies, nude mice bearing the human carcinomas were given Li[1-14C]GLA (2.5 mg kg-') by intravenous injection for 30 min. Mice were either sacrificed after infusion or left for up to 96 h recovery before sacrifice. In general, the organs showed a maximum uptake of radioactivity 30 min after the infusion started (t = 0). Thereafter, in major organs the percentage of injected radioactivity per g of tissue declined below 1% 96 h after infusion. In kidney, brain, testes/ovaries and all three tumour tissues, labelling remained constant throughout the experiment. The ratio of radioactivity in liver to tumour tissues ranged between 16-and 24-fold at t = 0 and between 3.1-and 3.7-fold at 96 h. All tissues showed a progressive increase in the proportion of radioactivity associated with AA with a concomitant decrease in radiolabelled GLA as the time after infusion increased. DGLA declined rapidly in liver and plasma, but at a much slower rate in brain and malignant tissue. Seventy-two hours after the infusion, GLA was only detected in plasma and tumour tissue. The sum of GLA + DGLA varied among tumour tissues, but it remained 2-4 times higher than in liver and plasma. In brain, DGLA is the major contributor to the sum of these fatty acids. Data showed that cytotoxic GLA and DGLA, the latter provided either by the host or by endogenous synthesis, remained in human tumours for at least 4 days.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

In vivo and in vitro biotransformation of the lithium salt of gamma-linolenic acid by three human carcinomas

Antueno¹,

Elliot²,

Ells³

et al. 1997

Br J Cancer

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“…In contrast, radiolabeled fatty acids (oleic, palmitic, etc.) are 40 -95% metabolized by 1-5 min of incubation with cultured cells (33, 60, 61) or tissues such as liver (62).…”

Section: L-fabp Expression Stimulates Uptake and Nuclear Distributionmentioning

confidence: 99%

Liver Fatty Acid-binding Protein Targets Fatty Acids to the Nucleus

Huang¹,

Starodub²,

McIntosh³

et al. 2002

Journal of Biological Chemistry

130

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Because the nuclear peroxisome proliferator-activated receptors (PPAR) 1 regulate expression of genes involved in fatty acid oxidation (PPAR␣) and adiposity (PPAR␥), it has been postulated that PPARs play important roles in diabetes, atherosclerosis, and obesity (reviewed in Refs. 1-6). In support of this hypothesis, fatty acid oxidation is diminished in PPAR␣ geneablated mice (7-9) accompanied by fat accumulation (heart (10), centrilobular regions of the liver (7, 8), adipose tissue (11)), hypercholesterolemia (12), and hypoglycemia (10). (13). These data strongly support the possibility that LCFAs may be natural ligands for PPARs and that LCFAs may be more specific ligands for PPAR␣ as compared with other PPARs. Unfortunately, physiological significance of these findings is not yet clear since it is not known whether unesterified, unbound LCFAs are present in the cell and that their concentration in the nucleus is at least in the nanomolar range.A variety of studies suggest that unesterified LCFAs are present within the cell at levels physiologically significant for regulating PPAR␣ activity. Based on the Michaelis constant of long chain fatty acyl-CoA synthetase, the total cellular unesterified LCFA concentration has been estimated near 20 M (18). However, because of the presence of intracellular fatty acid-binding proteins (FABPs) (reviewed in Ref. 19), the intracellular concentration of unbound, unesterified LCFAs is thought to be nearly 3 orders of magnitude lower, near 7-50 nM in liver, heart, and intestine (20, 21). Whether nuclear levels of unbound LCFAs are also in the nanomolar range is not known. Another key question is the origin of nuclear unesterified LCFAs. Nuclei do not synthesize LCFAs but must import them from the cytosol (22-24) by as yet unresolved transport systems. Nearly 20 and 4% of the plasma-derived unesterified LCFAs appear in nuclei isolated from hepatocytes (23) and cerebral cortex or leukemic lymphocytes (22, 24 -26), respectively. Despite data suggesting the presence of high (up to 40% of nuclear lipids) levels of unesterified LCFAs in isolated nuclei (27), subcellular fractionation studies may be complicated by LCFAs derived from lipolytic release, transfer from other intracellular sites, or cross-contamination with other mem-

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Incorporation and metabolic conversion of saturated and unsaturated fatty acids in SK-Hep1 human hepatoma cells in culture

Marra

Alaniz

1992

Mol Cell Biochem

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We report here a study of the incorporation and metabolism of various long chain fatty acids in SK-Hep-1 cultured hepatoma cells. Medium supplementation with radiolabelled palmitic, stearic, linoleic, alpha-linolenic and eicosa-8,11,14-trienoic acids (1 microM, 24 H) resulted in an active uptake of each of these precursors by the cultures. Subsequent analysis of the cellular lipids indicated that they exhibit almost all the enzymic activities of polyunsaturated fatty acid metabolism that are characteristic of normal hepatic cells. With respect to the desaturation capacities of this cell line, although alpha-linolenic acid reacted more extensively than did linoleic acid and the conversion of 8,11,14-eicosatrienoic acid by the delta 5 specific enzyme was more avid than had been previously seen in normal rat or human liver: the saturated fatty acids constituted relatively poor substrates, being preferentially chain-elongated rather than (mono) desaturated at the delta 9 position. Analysis of the fatty acid profiles of total cellular lipids and of various lipid subclasses, however, revealed a relative paucity of essential fatty acids when compared with the abundance of endogenous monoenoic acids (particularly oleic). Of the total cellular fatty acids, 58% were present in the form of phospholipids; with 33% of the remaining 42% (i.e., the neutral lipids) being associated with triacylglycerol fraction. Within the total lipids, phosphatidyl-choline and phosphatidyl-ethanolamine were the major sites for the incorporation of all metabolic products derived from the incubated radiolabelled 16- and 18-carbon fatty acid precursors, whereas the phosphatidyl-inositol fraction was the predominant recipient of nascent arachidonic acid when the eicosatrienoate was the substrate. The express purpose of this investigation was to characterize the biochemical routes involved in the anabolism of various essential fatty acids in the human hepatocyte, through the use of cultured human hepatoma cells as an experimental model system. In view of the similarities between certain aspects of the polyunsaturated fatty acid metabolism of these cells and the corresponding properties of other mammalian hepatic or liver-derived tissues, the data presented here would thus constitute a significant beginning alone those lines. Moreover, considering the extreme difficulty in obtaining for such investigation relevant tissue samples from normal human sources, we regard these results- and the availability for use of this particular human hepatoma cell line-as important new developments in the effort to characterize a useful experimental model both for gaining immediate information and for designing future experiments.

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Uptake and metabolism of free fatty acids by the morris 7777 hepatoma and host rat liver

Cited by 6 publications

References 19 publications

In vivo and in vitro biotransformation of the lithium salt of gamma-linolenic acid by three human carcinomas

In vivo and in vitro biotransformation of the lithium salt of gamma-linolenic acid by three human carcinomas

Liver Fatty Acid-binding Protein Targets Fatty Acids to the Nucleus

Incorporation and metabolic conversion of saturated and unsaturated fatty acids in SK-Hep1 human hepatoma cells in culture

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