Role of Δ9 desaturase activity in the maintenance of high levels of monoenoic fatty acids in hepatoma cultured cells

Abstract

The incorporation and delta 9 desaturation of exogenous [14C]stearic acid were studied in HTC 7288c cells in suspension. We examined the uptake of the acid over a wide range of concentrations (0-160 microM) after incubating the cells for 6 h in a chemically-defined medium. Under this experimental condition, the uptake of the labeled acid was more extensive than that obtained from static cultures or from monolayer of isolated hepatocytes of rats. At an external concentration of 160 microM ca. 52 nmoles of acid per mg of cellular protein was taken up. The production of oleic acid from [14C]stearate (delta 9 desaturation) correlated well with the uptake curve between 0-80 microM concentration. For higher stearate concentrations, the biosynthesis of oleic acid declined substantially and a plateau of 22 nmoles/mg cellular protein was reached. The incorporation and desaturation of an initial exogeneous concentration of [14C]stearic acid (80 microM) was also studied from 0-6 h. The results obtained demonstrated that the uptake of the substrate into cellular lipids was fast and non saturable. Quantitative gas-liquid chromatography of total cellular lipids under the different experimental conditions demonstrated a negative correlation between the decrease in the palmitic and palmitoleic acids and the increase in the intracellular levels of stearic and oleic acids. These analytical modifications took place with no changes in the saturated/monoenoic fatty acid ratio. This work also demonstrated a significant contribution of the stearoyl-CoA desaturase system to the high levels of oleic acid present in this kind of hepatoma cells.

Lipids changes in liver cancer

“…de Alaniz and Marra (1994) also demonstrated significant contribution of the stearoyl-CoA desaturase system to the high levels of oleic acid present in this kind of hepatoma cells. Peroxisome proliferators comprise a diverse group of chemicals which are regarded as rodent hepatocarcinogens and/or liver tumor promoters (Palut, 1997).…”

Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B1

“…In addition, the increased in MUFA, specifically C18:1x9 and C18:2x6 is associated with the disruption of the delta-6 desaturase enzyme known to be inhibited by FB 1 [30]. The resultant increase in MUFA could also be due to an increase in delta-9 desaturase as observed in tumour growth in mouse mammary carcinoma cells [70], hepatoma cells [71], human leukemia and lymphoma cells [72]. The growth of mammary carcinogenesis in vitro was blocked by the addition of an inhibitor of delta-9 desaturase [73].…”

Erythrocyte Membrane Fatty Acids and Subsequent Breast Cancer: a Prospective Italian Study

“…Several studies have suggested a link between ⌬9-d activity and tumor growth. Thus, high levels of MUFAs are required by mouse mammary carcinoma cells (18), hepatoma cells (33), and human leukemia and lymphoma cells (34). In all of these cases, the required MUFA levels are assured by overexpression of the genes encoding ⌬9-d. Inhibition of ⌬9-d and, consequently, of oleic acid biosynthesis blocks the growth of transplanted mammary tumor in rats (19).…”