The Hypoxic Microenvironment Induces Stearoyl-CoA Desaturase-1 Overexpression and Lipidomic Profile Changes in Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). It is characterized by a high cell proliferation and the ability to store lipids. Previous studies have demonstrated the overexpression of enzymes associated with lipid metabolism, including stearoyl-CoA desaturase-1 (SCD-1), which increases the concentration of unsaturated fatty acids in tumor cells. In this work, we studied the expression of SCD-1 in primary ccRCC tumors, as well as in cell lines, to determine its influence on the tumor lipid composition and its role in cell proliferation. The lipidomic analyses of patient tumors showed that oleic acid (18:1n-9) is one of the major fatty acids, and it is particularly abundant in the neutral lipid fraction of the tumor core. Using a ccRCC cell line model and in vitro-generated chemical hypoxia, we show that SCD-1 is highly upregulated (up to 200-fold), and this causes an increase in the cellular level of 18:1n-9, which, in turn, accumulates in the neutral lipid fraction. The pharmacological inhibition of SCD-1 blocks 18:1n-9 synthesis and compromises the proliferation. The addition of exogenous 18:1n-9 to the cells reverses the effects of SCD-1 inhibition on cell proliferation. These data reinforce the role of SCD-1 as a possible therapeutic target.

Radical scavenging activity of lipids from seaweeds isolated by solid-liquid extraction and supercritical fluids

In vitro antioxidant activities of the lipid fractions from two selected seaweeds, Solieria chordalis and Sargassum muticum were investigated according to the extraction methods. The activity of neutral lipids, glycolipids and phospholipids, thanks to extraction by chloroform/methanol (1/1 v/v; CM) mixture, pure supercritical carbon dioxide (sc-CO2), supercritical carbon dioxide with 2% of ethanol (sc-CO2 + EtOH 2%) and supercritical carbon dioxide with 8% of ethanol as co-solvent (sc-CO2 + EtOH 8%), were studied using DPPH radical scavenging assays. All the lipid classes demonstrated a free radical scavenging activity at the concentration of 1 mg/ml. The best scavenging activity (86.6 ± 5.7%) was obtained when the neutral lipid fraction was extracted from S. chordalis with a CM mixture. The neutral lipid fraction extracted with sc-CO2 showed a lower activity than those obtained with solvents. However, the addition of ethanol in sc-CO2 did not affect the antioxidant activity of neutral lipids fixed at around 16% of radical scavenging. For S. muticum, the activity of glycolipids (50.9 ± 0.8%) and phospholipids (48.4 ± 1.6%) obtained with sc-CO2 were twice as large as that of fractions obtained with CM, 29.6 ± 3.4% and 28.0 ± 4.2%, respectively. The activity of neutral lipids did not change with the extraction method with around 25% of radical scavenging. This is the first report of free radical scavenging activity of lipid classes obtained by supercritical carbon dioxide extraction from seaweeds.

Hepatotoxicity and Langerhans Islets Regenerative Effects of Polar and Neutral Lipids of Nigella sativa L. in Nicotinamide/streptozotocin-Induced Diabetic Rats

The extracted oil from Nigella sativa seeds is reported to be effective against various diseases and chemicallyinduced hepatotoxicity and nephrotoxicity. The effect of oral administration of Nigella sativa total, polar and neutral oils was investigated on hepatoprotective status in streptozotocin/nicotinamide (STZ-N)-induced diabetic rats. The toxicity was assessed biochemically by monitoring aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptitase (g-GT) and alkaline phosphatase (AP) activities as well as biluribin titre and histologically under light microscope. The study was also undertaken to evaluate the effect of oil fractions on the regeneration of pancreatic Langerhans islets in treated diabetic rats.Biochemical analysis showed that lipid fractions from total oil of Nigella sativa seeds are not hepatotoxic. However, histological study of the liver demonstrated major and minor tissue damages with the neutral fraction exhibiting the most protective effect. At the end of the experiment period (17 days) of treatment with thymoquinone (25mg/kg bw/day) or neutral lipid fraction (100mg/kg bw/day), a positive effect on the regenerative of Langerhans islets, initially distorted by STZ, was observed. Thus, the hypoglycaemic effect of neutral lipid fraction could be a result of the regeneration of the pancreatic Langerhans islets.

Neutral lipids, phospholipids, and a betaine lipid of the snow mold fungus Microdochium nivale

The hyphae of the snow mold Microdochium nivale contained lipids in a yield of about 10% w/w of the dry matter of hyphae. The total lipid was fractionated into neutral and polar lipid fractions. In the neutral lipid fraction, triacylglylcerol was the sole major component. As minor components, ergosterol, diacylglycerol, free fatty acid, and fatty acyl ergosterol were identified. The polar lipid fraction contained phospholipids, glycolipids, and a lipid containing neither phosphorus nor sugar. Phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, and phosphatidic acid were identified as phospholipids. The polar lipid fraction included at least four kinds of glycolipids that have not been identified. A very unusual lipid in fungi, a betaine lipid, diacylglyceryltrimethylhomoserine, was identified by chemical and physicochemical analyses. The level of the neutral lipid fraction, which accounted for 60% of the total lipid in hyphae at the exponential phase, was significantly increased compared with that of the polar lipid fraction and constituted 80% of the total at the stationary phase. The neutral and polar lipids of Microdochium nivale contained 18:3 (9,12,15), 18:2 (9,12), 18:1 (9), and 16:0 as principal fatty acids. Among them, 18:2 (9,12) and 18:3 (9,12,15) were the major fatty acids of triacylglycerol, phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine, whereas in diacylglyceryltrimethylhomoserine, the major components were 16:0 and 18:3 (9,12,15).Key words: snow mold, phospholipids, betaine lipid, fatty acid, Microdochium nivale.

The effect of long term storage on the lipid reserves and fatty acid composition of cysts and hatched juveniles of Globodera rostochiensis and G. pallida

The lipid composition of three batches of single generation cysts of Globodera rostochiensis, stored dry at 4°C for 1,7 and 13 years, comprised 81%, 74% and 53% neutral lipids, 14%, 18% and 27% non-acidic phospholipids and 5%, 8% and 20% free fatty acids, respectively. Lipids in eggs from two batches of G. pallida cysts, stored for 3 and 7 years, comprised 80% and 67% neutral lipids, 15% and 23% non-acidic phospholipids and 5% and 10% free fatty acids, respectively. All batches contained the same fatty acids which were dominated by C18:l, C20:l and C20:4. The fatty acid profiles of hatched J2 of G. rostochiensis from two batches, stored for 1 and 9 years, differed only in their free fatty acid fractions. Thus, while it is not possible to determine the age of cysts by their fatty acid profile, it may be possible to use the relative amounts of the main lipid classes as an indicator of age. Four batches of hatched J2 of G. pallida were investigated, with sample A hatched during the second week in potato root diffusate, B during week 3, C during week 4 and D during weeks 5 and 6 and stored for 3.5 days (on average) after hatching. Total lipid content was 27.2%, 31.5%, 18.5% and 6.3% of the dry weight for A, B, C and D, respectively. In the neutral lipid fraction of D an increase in C18:l and to a lesser extent C18:2 was observed. In the free fatty acid fraction of sample D, the percentages of C18:l, C18:2 and C18:3 were greater but the percentages of C20:3 and C20:4 were smaller compared with sample C. Fresh early hatched J2 of G. rostochiensis were compared with later hatched and stored (for 13 days on average) individuals for their lipid content and fatty acid composition. The lipid content was 26.1% and 11.4% in fresh and stored J2, respectively. Total lipid consisted of 77% and 70% neutral lipid, 18% and 26% non-acidic phospholipid and 6% and 4% free fatty acid in fresh and stored J2, respectively. In the neutral lipid fraction of stored J2 C18:l, C16:0 and C18:0 increased, whereas C20:4, C20:l and C20:3 decreased. Therefore, both neutral lipid and free fatty acid fractions showed changes in their fatty acid profiles after long delayed hatching and/or storage in both PCN species.

Variations du contenu lipidique occasionnées par la carence en pyridoxine du milieu nutritif de Ceratocystis ulmi

Pyridoxin deficiency of the synthetic growth medium results on four of the five strains of the studied Ceratocystis ulmi in an increase (6.9 to 18.8%) of the lipid content of the mycelium. This increase mainly affects the neutral lipid fraction. The analysis of fatty acids shows a significative decrease, both in the neutral and the polar lipid fraction, of the polyunsaturated fatty acid content, and in some cases the total disappearance of the linolenic acid.