Nonsaponifiable Lipids Research Articles

Effects of dietary use of two lipid extracts from the microalga Nannochloropsis gaditana (Lubián, 1982) alone and in combination on growth and muscle composition in juvenile gilthead seabream, Sparus aurata

Microalgae are a source of diverse high-value compounds, such as carotenoids and fatty acids, which have a potential application in aquafeeds. Some microalgae species present complex cell wall structures, which make them poorly digestible, thus limiting their use as a feed ingredient. Consequently, applying extracted compounds to aquafeeds instead of using the whole algal biomass is advantageous as this is expected to increase the bioavailability of these nutrients. The aim of this study was to evaluate the effect of the dietary inclusion (2%) of two extracts obtained from the microalga Nannochloropsis gaditana (one composed of saponifiable lipids and the other of non-saponifiable lipids), alone or in combination, on growth, muscle composition, skin color and lipid oxidation in juvenile gilthead seabream, Sparus aurata, following a 39-day trial. Overall, the inclusion of 2% of the saponifiable lipid extract did not affect the growth performance but fish muscle presented a lower percentage of docosahexaenoic acid (DHA) and a higher eicosapentaenoic acid (EPA) than that of the fish fed the diets lacking this lipidic fraction. Despite no effect being observed in fish growth performance, the inclusion of 2% of the non-saponifiable lipid extract enhanced the carotenoid content of the fish muscle, which prevented lipid oxidation, and modulated the skin pigmentation towards a yellow-greenish color. The present study confirms the success of applying both high-value microalgae lipidic extracts, alone or in combination, as feed additives for practical diets in juvenile gilthead seabream.

Trophic upgrading and mobilization of wax esters in microzooplankton.

Heterotrophic protists play pivotal roles in aquatic ecosystems by transferring matter and energy, including lipids, from primary producers to higher trophic predators. Using Oxyrrhis marina as a model organism, changes to the non-saponifiable protist lipids were investigated under satiation and starvation conditions. During active feeding on the alga Cryptomonas sp., the O. marina hexane soluble non-saponifiable fraction lipid profile reflected its food source with the observed presence of long chain mono-unsaturated fatty alcohols up to C25:1. Evidence of trophic upgrading in O. marina was observed with long chain mono-unsaturated fatty alcohol accumulation of up to C35:1. To the best of our knowledge, this is the first evidence that heterotrophic dinoflagellates are capable of producing ester derived alcohols and that dinoflagellates like O. marina are capable of synthesizing fatty alcohols up to C35. Additionally, we show evidence of trophic upgrading of lipids. During a 20-day resource deprivation, the lipid profile remained constant. During starvation, the mobilization of wax esters as energy stores was observed with long chain fatty alcohols mobilized first. Changes in lipid class profile and utilization of wax esters in O. marina provides insight into the types of lipids available for energy demand, the transfer of lipids through the base of marine food webs, and the catabolic response induced by resource deprivation.

Sterol Analysis in Kluyveromyces lactis.

Sterols are essential lipids of most eukaryotic cells with multiple functions (structural, regulatory and developmental). Sterol profile of yeast cells is often determined during the studies of ergosterol synthesis mutants used to uncover a number of functions for various sterols in yeast cells. Molecular studies of ergosterol biosynthesis have been also employed to identify essential steps in the pathway against which antifungals might be developed. We present here a protocol for the isolation of non-saponifiable lipids (sterols) from Kluyveromyces lactis yeast cells and a chromatographic method for quantitative analysis of sterols in lipid extracts (HPLC) that can be performed in laboratories with standard equipment.

Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by Lippia alba Essential Oils.

The essential oils (EOs) of Lippia alba, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that L.alba EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four L. alba chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP). [14C]Acetate was used as radioactive precursor for assays. Lipid analyses were performed by thin-layer and capillary gas chromatography, lipid droplets analyzed by fluorescence microscopy, and HMGCR levels determined by Western blot. In both cell lines, all four chemotypes exerted hypocholesterogenic effects within a concentration range of 3.2-32µg/mL. Nonsaponifiable lipids manifested a decrease in incorporation of [14C]acetate into squalene, lanosterol, lathosterol, and cholesterol, but not into ubiquinone, thus suggesting an inhibition of enzymes in the MP downstream from farnesyl pyrophosphate. The tagetenone chemotype, the most efficacious hypocholesterogenic L. alba EO, lowered HMGCR protein levels; inhibited triacylglycerols, cholesteryl esters, and phospholipids synthesis; and diminished lipid droplets in size and volume. These results revealed that L. alba EOs inhibited different lipogenic pathways and such lipid-lowering effects could prove essential to prevent cardiovascular diseases.

4-Methylzymosterone and Other Intermediates of Sterol Biosynthesis from Yeast Mutants Engineered in the ERG27 Gene Encoding 3-Ketosteroid Reductase.

Studies in the post-squalene section of sterol biosynthesis may be hampered by the poor availability of authentic standards. The present study used different yeast strains engineered in 3-ketosteroid reductase (Erg27p) to obtain radioactive and non-radioactive intermediates of sterol biosynthesis hardly or not available commercially. Non-radioactive 3-keto 4-monomethyl sterones were purified from non-saponifiable lipids extracted from cells bearing point-mutated 3-ketosteroid reductase. Two strategies were adopted to prepare the radioactive compounds: (1) incubation of cell homogenates of an ERG27-deletant strain with radioactive lanosterol, (2) incubation of growing cells of a strain expressing point-mutated 3-ketosteroid reductase with radioactive acetate. Chemical reduction of both radioactive and non-radioactive 3-keto sterones gave the physiological 3-β OH sterols, as well as the non-physiological 3-α OH isomers. This combined biological and chemical preparation procedure provided otherwise unavailable or hardly available 4-mono-methyl intermediates of sterol biosynthesis, paving the way for research into their roles in physiological and pathological conditions.

Biodiesel synthesis by direct transesterification of microalga Botryococcus braunii with continuous methanol reflux

Direct transesterification of Botryococcus braunii with continuous acyl acceptor reflux was evaluated. This method combines in one step lipid extraction and esterification/transesterification. Fatty acid methyl esters (FAME) synthesis by direct conversion of microalgal biomass was carried out using sulfuric acid as catalyst and methanol as acyl acceptor. In this system, once lipids are extracted, they are contacted with the catalyst and methanol reaching 82%wt of FAME yield. To optimize the reaction conditions, a factorial design using surface response methodology was applied. The effects of catalyst concentration and co-solvent concentration were studied. Hexane was used as co-solvent for increasing lipid extraction performance. The incorporation of hexane in the reaction provoked an increase in FAME yield from 82% (pure methanol) to 95% when a 47%v/v of hexane was incorporated in the reaction. However, the selectivity towards non-saponifiable lipids such as sterols was increased, negatively affecting biodiesel quality.

Characterization of the liposoluble fraction of common wheat (Triticum aestivum ) and spelt (T. aestivum ssp. spelta ) flours using multivariate analysis

In the present paper, a special method for derivatization of liposoluble extract of common wheat and spelt flours was employed which enables simultaneous detection of fatty acid and non-saponifiable lipid fractions. Gas chromatographic-mass spectrometric analytical data for both fractions were separately analyzed by multivariate statistical techniques to model classes of different common wheat and spelt cultivars. Cluster analysis was used, and the results obtained revealed that better discrimination of samples was achieved by analyzing the peak area after 16 min retention time (non-saponifiable lipids), rather than commonly used peak area between 12 and 16 min (fatty acid fraction), due to more distinctive positions of points in factor space, even though the distances between points for fatty acid fraction (12-16 min) were greater. Similar results were obtained by principal components analysis, where all wheat points almost coincided whereas spelt showed good discrimination. Comparison of chromatogram areas for non-saponifiable lipid fraction between common and spelt wheat showed a statistically high difference and hence has a potential for use in authenticity control.

A possibility of determining the authenticity of organic wheat using GC-MS

Qualitative analysis of liposoluble wheat extract from conventional, integrated, organic, biodynamic and control farming systems was performed by gas chromatography with mass spectrometry (GC-MS). Organic and biodynamic farming systems were close to each other versus conventional and integrated which are similar in fertilization and plant protection. In the control treatment no fertilization or plant protection was used. Cluster analysis (CA) was applied to classify the samples according to lipid profiles in wheat from different farming systems. The obtained results showed that better discrimination of wheat samples was achieved by analyzing the peak area after 18 min retention time (non-saponifiable lipid fraction), than used the peak area for the whole chromatogram. The study has found that this method can be a potentially used for making a distinction between organic and non-organic wheat production.

Initial studies on squalene from some marine microalgae isolated in Vietnam

Squalene is a highly unsaturated aliphatic hydrocarbon and belongs to the triterpene group of oils. Squalene is the last metabolite preceding sterol ring formation in the biosynthetic cholesterol pathway. It is normally used in its natural form as a moisturizing or emollient agent in pharmaceuticals and cosmetic preparations. More importantly, it is a potential oxidation inhibitor; it can protect cell against free radicals, strengthen the body’s immune system and decrease the risk for various cancers. In this study, we presented the results of initial research on squalene from seven marine microalgal species isolated in Vietnam coasts. Based on colorimetric method, squalene content in these microalgae was determined. Schizochytrium mangrovei reached the highest squalene content of 122 mg/g. Squalene content of 21.090 mg/g for Thraustochytrium mangrovei, 6.300 mg/g for Dunaliella tetiolecta, 9.700 mg/g for Isochrysis galbana, 0.193 mg/g Nannochloropsis oculata, 1.850 mg/g for Tetraselmis convolutae and 3.300 mg/g for Chlorella vulgaris were obtained. Moreover, thin layer chromatography and high performance liquid chromatography methods were successfully applied to the determination of squalene in S. mangrovei. The squalene content of S. mangrovei analysed by TLC and HPLC reached 12.630 mg/g of nonsaponifiable lipid, 0,405 mg/g of total lipid and 0,203 mg/g of dry biomass.

Non-Saponifiable Lipid Composition of Four Salt-Secretor and Non-Secretor Mangrove Species from North Sumatra, Indonesia

Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Non-saponifiable lipid (NSL) of the fresh leaves and roots from two salt-secretor mangrove species, namely Aegiceras corniculatum (L.) Blanco and Avicennia alba Bl. and two non-secretor mangroves, i.e. Acrostichum aureum L. and Excoecaria agallocha L. was analyzed with special emphasize to triterpenoids and phytosterols. Identification of the triterpenoids and phytosterols was confirmed by comparison of their retention time on the GC column with those of authentic standards and on the interpretation of GC-MS spectra. Triterpenoids and phytosterols comprised the major proportion of NSL. The triterpenoids and phytosterols mainly consisted of 7 and 4 compounds. Triterpenoids were the largest constituent of Ac. aureum and Ae. corniculatum leaves and roots, and E. agallocha roots. In contrast to these triterpenoids-rich species, phytosterols were relatively dominant in the roots of Av. alba . The species of Av. alba and E. agallocha in the leaves were distinguished from the others in that both species contained a larger quantity of phytol. Ae. corniculatum contained a large amount of betulin and α-amyrin in the roots, as well as lupeol in the roots of Av. alba . The diversity in the NSL composition noted with mangrove species in both the leaves and roots suggested that NSL of mangroves was chemotaxonomically significant between the species. Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Keywords: leaf, mangrove, phytosterol, triterpenoid, root

Effects of antisense-mediated inhibition of 11β-hydroxysteroid dehydrogenase type 1 on hepatic lipid metabolism

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) converts inactive 11-keto derivatives to active glucocorticoids within tissues and may play a role in the metabolic syndrome (MS). We used an antisense oligonucleotide (ASO) to knock down 11β-HSD1 in livers of C57BL/6J mice consuming a Western-type diet (WTD). 11β-HSD1 ASO-treated mice consumed less food, so we compared them to ad libitum-fed mice and to food-matched mice receiving control ASO. Knockdown of 11β-HSD1 directly protected mice from WTD-induced steatosis and dyslipidemia by reducing synthesis and secretion of triglyceride (TG) and increasing hepatic fatty acid oxidation. These changes in hepatic and plasma lipids were not associated with reductions in genes involved in de novo lipogenesis. However, protein levels of both sterol regulatory element-binding protein (SREBP) 1 and fatty acid synthase were significantly reduced in mice treated with 11β-HSD1 ASO. There was no change in hepatic secretion of apolipoprotein (apo)B, indicating assembly and secretion of smaller apoB-containing lipoproteins by the liver in the 11β-HSD1-treated mice. Our results indicate that inhibition of 11β-HSD1 by ASO treatment of WTD-fed mice resulted in improved plasma and hepatic lipid levels, reduced lipogenesis by posttranslational regulation, and secretion of similar numbers of apoB-containing lipoproteins containing less TG per particle.

Validation of a gas–liquid chromatographic method for analysing samples rich in long chain n−3 polyunsaturated fatty acids: Application to seafood

Seafood, in general, contains high levels of long chain n−3 polyunsaturated fatty acids (LC n−3 PUFAs), and its consumption has been shown to have positive effects on human health. A method previously reported to be highly effective for PUFA analysis in beef, based on saponification, double extraction and methylation by trimethylsilyl-diazomethane, was validated for seafood fatty acid (FA) determination. The method could be highly suitable for FA analysis in marine tissues since it has shown higher effectiveness in PUFA analysis than classic methods, avoids the production of base-catalyzed artifacts and removes non-saponifiable lipids from the sample. The method was evaluated on three seafood matrices: molluscs ( Chamelea gallina), crustaceans ( Parapenaeus longirostris) and fish ( Pagellus bogaraveo), and 10 FAs representative of seafood were used. Overall recovery values from the three matrices ranged from 80% to 107%. Intra-day RSD ranged between 0.5% and 7.2%, with an average value of 3.4%, while inter-day RSD values ranged between 1.1% and 9.7%, with an average value of 5.7%. Consistent recovery and RSD values were obtained and the method was deemed to produce acceptable accuracy. The applicability of the method to the determination of total FAs in samples rich in LC n−3 PUFA, as seafood products, was demonstrated.

Inhibition of ergosterol synthesis by novel antifungal compounds targeting C-14 reductase

The limited number of clinically available antifungal drugs for life-threatening fungal infections has produced an increased demand for new agents. In the course of our screening for novel antifungals, we identified aminopiperidine derivatives which exhibit antifungal activities against the major pathogenic yeasts. Thin layer chromatography (TLC) analysis of the extracted non-saponifiable lipids from Candida albicans showed that these compounds inhibited the ergosterol production in the late step of the synthesis pathway. The results of an LC/Q-Tof MS analysis showed that abnormal sterols including predicted ignosterol, which is known to be accumulated in C. albicans ERG24 deleted mutant, were accumulated in C. albicans treated with one of these derivatives (Compound 1b). Furthermore, the partial disruption of the cell membrane of C. albicans treated with compound 1b was observed by electron microscopy analysis, suggesting its inhibition of ergosterol synthesis. Additionally, a genetic approach demonstrated that ERG24 gene would be responsible for the resistance of Saccharomyces cerevisiae against Compound 1b, strongly indicating that the enzyme targeted by Compound 1b is Erg24p. From all these data, we concluded that these aminopiperidine derivatives are novel antifungal compounds inhibiting C-14 reduction in the ergosterol synthesis pathway.

Triterpene Alcohol and Fatty Acid Composition of Shea Nuts from Seven African Countries

The content and composition of triterpene alcohol fractions of the non-saponifiable lipids (NSL) along with the fatty acid composition of the kernel fats (n-hexane extracts) of the shea tree (Vitellaria paradoxa; Sapotaceae) were determined for 36 samples from seven sub-Saharan countries: Cote d' Ivoire, Ghana, Nigeria, Cameroun, Chad, Sudan, and Uganda. The fat content of the kernels, proportion of NSL in the fats, and triterpene alcohols in the NSL are in the range of 30-54, 2-12, and 22-72%, respectively. The triterpene alcohol fractions contained alpha-amyrin (1), beta-amyrin (2), lupeol (3), and butyrospermol (4) as the major constituents along with minor or trace amounts of psi-taraxasterol (5), taraxasterol (6), parkeol (7), 24-methylene-24-dihydroparkeol (8), 24-methylenecycloartanol (9), dammaradienol (10), and 24-methylenedammarenol (11). Fatty acid composition is dominated by stearic (28-56%) and oleic (34-61%) acids. Shea butters from West African provenances contained in general higher levels of triterpene alcohols and stearic acid than those from East African provenances. Both stearic acid and total triterpene alcohol contents were significantly correlated to the latitude and elevation of the source population, indicating that higher levels of these compounds are found at higher ambient temperatures.

Phenanthrene Sorption by Fruit Cuticles and Potato Periderm with Different Compositional Characteristics

Phenanthrene sorption by fruit cuticles (tomato, apple, and grape), potato tuber periderm, and their fractions were investigated to elucidate effects of compositional characteristics on affinity of plant cuticle (above-ground) and periderm (below-ground) with hydrophobic organic contaminants (HOCs). The distinct roles of the extractable lipids (waxes), the depolymerizable lipids (cutin/suberin), the nonsaponifiable lipids (cutan/suberan) and polysaccharide are discussed. The cutin/suberin rather than waxes dominates the sorption properties of bulk cuticle/periderm, but the sorption coefficient (K(d)) is linearly correlated with the total lipid contents. Polysaccharide plays a negative role in HOC sorption due to its obviously poor affinity with HOCs and restriction effect on the other powerful sorptive regions in cuticle/periderm. The significantly lower sorption of periderm than cuticle is attributed to the former having higher polysaccharide and lower depolymerizable lipids. The linear correlation of K(d) of bulk cuticle/periderm with polysaccharide content is observed for a potential prediction of plant uptake.

Isoprenoids of Okinawan mangroves as lipid input into estuarine ecosystem

Isoprenoids in the nonsaponifiable lipids (NSL) fraction of Okinawan mangroves were analyzed with special reference to their importance as lipid input into estuarine ecosystems. Triterpenoids and phytosterols comprised the major proportion of NSL. Identifications of the triterpenoids and phytosterols in NSL fraction were based on the interpretation of 13 C-NMR and GC-MS spectra. The triterpenoids and phytosterols mainly comprised 11 and 6 compounds, respectively. The major components were lupeol, β-amyrin and taraxerol for triterpenoids, and β-sitosterol and stigmasterol for phytosterols. The diversity in the terpenoid composition was noted in both leaves and roots of mangrove species, implying the chemotaxonomic utility of terpenoids. Terpenoid compositions of the root are not always similar to that of leaf, suggesting that terpenoids in the root are produced by biosynthesis in situ, not by translocation of the synthate from the leaf. Terpenoids existed in greater proportion in the outer parts of the root. These data are likely to contribute to estimating the lipid input from mangrove trees adjacent to estuarine sediments and the ocean.

Fast and easy in vitro screening assay for cholesterol biosynthesis inhibitors in the post-squalene pathway

A whole-cell assay for screening cholesterol biosynthesis inhibitors in the post-squalene pathway has been developed. HL 60 cells were incubated for 24 h with test substances. The nonsaponifiable lipids were extracted by means of liquid–liquid extraction using tert-butylmethylether. The raw extracts were purified by dispersive solid phase extraction using a primary–secondary amine material (PSA) and dried using sodium sulphate. The sterols were derivatized using N-trimethylsilylimidazole. GLC/MS analysis was carried out in less than 12.5 min using fast GLC mode. The obtained sterol patterns indicated which enzyme had been inhibited. Specific sterol patterns which reflect the different enzyme inhibitions were obtained using established inhibitors of cholesterol biosynthesis like AY 9944, NB 598, clotrimazole, aminotriazole and DR 258, a Δ24-reductase inhibitor prepared in our working group. For characterizing IC 50 values we used sodium 2- 13C-acetate and quantified the incorporation of it into cholesterol relative to control levels after the samples had been normalized to their protein content.

Regulation of intestinal NPC1L1 expression by dietary fish oil and docosahexaenoic acid

To address the effect of the n-3 fatty acid, docosahexaenoic acid (22:6), on proteins that play a role in cholesterol absorption, CaCo-2 cells were incubated with taurocholate micelles alone or micelles containing 22:6 or oleic acid (18:1). Compared with controls or 18:1, 22:6 did not interfere with the cellular uptake of micellar cholesterol. Apical cholesterol efflux was enhanced in cells incubated with 22:6. Cholesterol trafficking from the plasma membrane to the endoplasmic reticulum was decreased by 22:6. 22:6 decreased Niemann-Pick C1-Like 1 (NPC1L1) protein and mRNA levels without altering gene or protein expression of ACAT2, annexin-2, caveolin-1, or ABCG8. Peroxisome proliferator-activated receptor delta (PPARdelta) activation decreased NPC1L1 mRNA levels and cholesterol trafficking to the endoplasmic reticulum, suggesting that 22:6 may act through PPARdelta. Compared with hamsters fed a control diet or olive oil (enriched 18:1), NPC1L1 mRNA levels were decreased in duodenum and jejunum of hamsters ingesting fish oil (enriched 22:6). In an intestinal cell, independent of changes in ABCG8 expression, 22:6 increases the apical efflux of cholesterol. 22:6 interferes with cholesterol trafficking to the endoplasmic reticulum by the suppression of NPC1L1, perhaps through the activation of PPARdelta. Moreover, a diet enriched in n-3 fatty acids decreases the gene expression of NPC1L1 in duodenum and jejunum of hamster.

Plant sterol or stanol esters retard lesion formation in LDL receptor-deficient mice independent of changes in serum plant sterols

Statins do not always decrease coronary heart disease mortality, which was speculated based on increased serum plant sterols observed during statin treatment. To evaluate plant sterol atherogenicity, we fed low density lipoprotein-receptor deficient (LDLr(+/-)) mice for 35 weeks with Western diets (control) alone or enriched with atorvastatin or atorvastatin plus plant sterols or stanols. Atorvastatin decreased serum cholesterol by 22% and lesion area by 57%. Adding plant sterols or stanols to atorvastatin decreased serum cholesterol by 39% and 41%. Cholesterol-standardized serum plant sterol concentrations increased by 4- to 11-fold during sterol plus atorvastatin treatment versus stanol plus atorvastatin treatment. However, lesion size decreased similarly in the sterol plus atorvastatin (-99% vs. control) and the stanol plus atorvastatin (-98%) groups, with comparable serum cholesterol levels, suggesting that increased plant sterol concentrations are not atherogenic. Our second study confirms this conclusion. Compared with lesions after a 33 week atherogenic period, lesion size further increased in controls (+97%) during 12 more weeks on the diet, whereas 12 weeks with the addition of plant sterols or stanols decreased lesion size (66% and 64%). These findings indicate that in LDLr(+/-) mice 1) increased cholesterol-standardized serum plant sterol concentrations are not atherogenic, 2) adding plant sterols/stanols to atorvastatin further inhibits lesion formation, and 3) plant sterols/stanols inhibit the progression or even induce the regression of existing lesions.

Effect of geraniol on fatty-acid and mevalonate metabolism in the human hepatoma cell line Hep G2

Monoterpenes have multiple pharmacological effects on the metabolism of mevalonate. Geraniol, a dietary monoterpene, has in vitro and in vivo anti-tumor activity against several cell lines. We have studied the effects of geraniol on growth, fatty-acid metabolism, and mevalonate metabolism in the human hepatocarcinoma cell line Hep G2. Up to 100 micromol geraniol/L inhibited the growth rate and 3-hydroxymethylglutaryl coenzyme A reductase (HMG-CoA) reductase activity of these cells. At the same concentrations, it increased the incorporation of cholesterol from the medium in a dose-dependent manner. Geraniol-treated cells incorporated less 14C-acetate into nonsaponifiable lipids, inhibiting its incorporation into cholesterol but not into squalene and lanosterol. This is indicative of an inhibition in cholesterol synthesis at a step between lanosterol and cholesterol, a fact confirmed when cells were incubated with 3H-mevalonate. The incorporation of 3H-mevalonate into protein was also inhibited, whereas its incorporation into fatty acid increased. An inhibition of delta5 desaturase activity was demonstrated by the inhibition of the conversion of 14C-dihomo-gamma-linolenic acid into arachidonic acid. Geraniol has multiple effects on mevalonate and lipid metabolism in Hep G2 cells, affecting cell proliferation. Although mevalonate depletion is not responsible for cellular growth, it affects cholesterogenesis, protein prenylation, and fatty-acid metabolism.