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Numerous studies have shown that high olive oil intake reduces blood pressure (BP). These positive effects of olive oil have frequently been ascribed to its minor components, such as ␣-tocopherol, polyphenols, and other phenolic compounds that are not present in other oils. However, in this study we demonstrate that the hypotensive effect of olive oil is caused by its high oleic acid (OA) content (Ϸ70 -80%). We propose that olive oil intake increases OA levels in membranes, which regulates membrane lipid structure (HII phase propensity) in such a way as to control G protein-mediated signaling, causing a reduction in BP. This effect is in part caused by its regulatory action on G protein-associated cascades that regulate adenylyl cyclase and phospholipase C. In turn, the OA analogues, elaidic and stearic acids, had no hypotensive activity, indicating that the molecular mechanisms that link membrane lipid structure and BP regulation are very specific. Similarly, soybean oil (with low OA content) did not reduce BP. This study demonstrates that olive oil induces its hypotensive effects through the action of OA.aorta ͉ fatty acids ͉ membrane structure ͉ signaling proteins ͉ membrane-lipid therapy

Polyunsaturated fatty acids (PUFA) are essential structural components of the central nervous system. Their role in controlling learning and memory has been well documented. A nutrigenomic approach with high-density microarrays was used to reveal brain gene-expression changes in response to different PUFA-enriched diets in rats. In aged rats fed throughout life with PUFA-enriched diets, genes with altered expressions included transthyretin, ␣-synuclein, and calmodulins, which play important roles in synaptic plasticity and learning. The effect of perinatal omega-3 PUFA supply on gene expression later in life also was studied. Several genes showed similar changes in expression in rats fed omega-3-deficient diets in the perinatal period, regardless of whether they or their mothers were fed omega-3 PUFA-sufficient diets after giving birth. In this experiment, among the down-regulated genes were a kainate glutamate receptor and a DEAD-box polypeptide. Among the up-regulated genes were a chemokine-like factor, a tumor necrosis factor receptor, and cytochrome c. The possible involvement of the genes with altered expression attributable to different diets in different brain regions in young and aged rats and the possible mode of regulatory action of PUFA also are discussed. We conclude that PUFA-enriched diets lead to significant changes in expression of several genes in the central nervous tissue, and these effects appear to be mainly independent of their effects on membrane composition. The direct effects of PUFA on transcriptional modulators, the downstream developmentally and tissue-specifically activated elements might be one of the clues to understanding the beneficial effects of the omega-3 PUFA on the nervous system.

The mechanism of action of 2-hydroxyoleic acid (2OHOA), a potent antitumor compound, has not yet been fully elucidated. Here, we show that human cancer cells have markedly lower levels of sphingomyelin (SM) than nontumor (MRC-5) cells. In this context, 2OHOA treatment strongly augments SM mass (4.6-fold), restoring the levels found in MRC-5 cells, while a loss of phosphatidylethanolamine and phosphatidylcholine is observed (57 and 30%, respectively). The increased SM mass was due to a rapid and highly specific activation of SM synthases (SMS). This effect appeared to be specific against cancer cells as it did not affect nontumor MRC-5 cells. Therefore, low SM levels are associated with the tumorigenic transformation that produces cancer cells. SM accumulation occurred at the plasma membrane and caused an increase in membrane global order and lipid raft packing in model membranes. These modifications would account for the observed alteration by 2OHOA in the localization of proteins involved in cell apoptosis (Fas receptor) or differentiation (Ras). Importantly, SMS inhibition by D609 diminished 2OHOA effect on cell cycle. Therefore, we propose that the regulation of SMS activity in tumor cells is a critical upstream event in 2OHOA antitumor mechanism, which also explains its specificity for cancer cells, its potency, and the lack of undesired side effects. Finally, the specific activation of SMS explains the ability of this compound to trigger cell cycle arrest, cell differentiation, and autophagy or apoptosis in cancer cells.anticancer | membrane-lipid therapy | lung cancer | membrane lipids T he potent antitumor compound 2-hydroxyoleic acid (2OHOA) (Minerval®) acts against cancer by inducing cell cycle arrest (1-3), followed by apoptosis in human leukemia cells (4) or differentiation and autophagy in the case of human glioma cells. Despite the potency of 2OHOA against cancer, it is a safe nontoxic compound with IC 50 values in nontumor cells 30-to 150-fold greater than in tumor cells (4). The high efficacy and low toxicity of this fatty acid produce a wide therapeutic window that can only be the consequence of a highly specific mechanism of action, the molecular bases of which have, in part, been elucidated here.The 2OHOA compound was designed rationally to reproduce the antitumor effect of anthracyclines via interactions with the plasma membrane and the ensuing modifications in cell signaling (5), without unspecific interactions with other cell targets. It is known that 2OHOA binds to membranes and modifies the biophysical properties of the lipid bilayer, the first target encountered by this synthetic lipid (6). Nevertheless, the regulatory effects of 2OHOA on the composition of cancer cell membranes have yet to be described. In fact, 2OHOA induces changes in the localization and activity of membrane proteins involved in cancer cell proliferation, differentiation and survival, such as the Fas receptor (4), PKC (3), as well as cyclins, cyclin-dependent kinases (CDKs), caspases, E2F-1 and dihydrofolate reductase...

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The compositions and physical states of the Iver phospholipids of marine and freshwater fish adapted to relatively constant but radically different temperatures were investigated. Fish adapted to low temperature (5-10°C) accumulated more unsaturated fatty acids than those in a warm (25-27°C) environment. There were no measurable differences in the gross fatty acid compositions of the total liver phospholipids fom Ident thermal environments. Docosahexaenoic acid (22:6) Poikilotherms are often subjected to temperature stress or seasonal variation of temperature. These organisms exploit diversity in lipid structures to fashion membranes to prevailing ambient temperatures in such a manner that they become more fluid in a cold-acclimatized state and less fluid in a warmth-acclimatized state (1, 2). Sinensky (3) has termed this response to temperature "homeoviscous adaptation". The extent ofhomeoviscous efficacy with which cells compensate membrane fluidity in response to changes in ambient temperature is only partial (4,5). However, this response is rather rapid in the carp liver endoplasmic reticulum (6) and erythrocytes (7). Restructuring of the polar headgroup composition of phospholipid classes, together with modification of the unsaturation of their fatty acyl chains, may ensure that the components present are best suited to function within the constraints imposed by a prevailing thermal environment. One rational explanation of these responses is that the melting points of the fatty acids decrease with an increasing number of double bonds in the molecule, resulting in a more fluid structure in membranes rich in polyunsaturated fatty acids. Accepting this hypothesis, one would expect a marked difference between fish species inhabiting regions of ex-The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.tremely different but relatively constant temperatures. Phospholipids from specific membranes of an Arctic marine fish proved more unsaturated than those of subtropical freshwater fish, and these differences were reflected in the microviscosity ofthese structures (8). The present article compares the liver phospholipid compositions of a number of marine and freshwater fish, and a feasible mechanism is proposed to explain the adaptational phenomena at a membrane structural level.MATERIALS AND METHODS Fish. The following fish were involved in this study. Warm-adapted marine fish (WAMF) included Carnax calla, Epinephelus bleekeri, Lutaganus sebeae, Mugil passia, Nemipterus hexodon, Nemipterusjavonicus, Pomadysys hasta, Sardinella longiceps, and Tachisurus yella from the South China Sea and the southwest coast of India (20-27C). Cold-adapted marine fish (CAMF) included Clupea harengus, Scorpaenichthys marmoratus, Hexaganus stelleri, Hipoglossus hipoglossus, Onchorhyncus kisutch, Onchorhyncus tshawsytscha, Ophioidon melanus, and Sebastosomus melanus from the...

Duplicate groups of small coho salmon and rainbow trout were fed a water‐soluble vitamin test diet containing 0, 5, 10, 20, 40 or 100 mg of ascorbic acid per 100 g of dry diet. Both salmon and trout fed deficient diets developed acute lordosis or scoliosis with resultant high mortality. Rainbow trout appeared to exhaust ascorbic acid reserves more rapidly than coho salmon. Blood levels of ascorbate reflected diet content of vitamin C at lower levels of intake and anterior kidney tissue content increased directly with C level in diet. Wound repair was delayed or inhibited in fish on low C diets and results generally supported diet and tissue levels needed for rapid growth and absence of histopathology. A dietary need for vitamin C for both species was evident.

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