Linoleic acid actions/effects

Toki et al. (72,73) have shown that certain amides of linoleic acid are effective in reducing the severity of cholesterol-induced atherosclerosis in rabbits. Their mechanism of action appears to involve inhibition of cholesterol absorption (74-76). Liver mitochondrial preparations from rats fed either linolexamide, A -cyclohexyl linoleamide (77) or AC-223, A-(a-meth-ylbenzyl)linoleamide (76) do not oxidize more cholesterol-26- C to i C02 than do similar preparations from livers of control rats. Table II summarizes the effects of these drugs on mitochondrial oxidation of cholesterol. It should be emphasized again that this system is of interest primarily because the proper enzyme system (for cholesterol side-chain cleavage) is involved. For a completely accurate assessment of this system, 3a,7a,12a-trihydroxycopros-tane would be the proper substrate. 

Belury, M.A. 2002. Dietary conjugated linoleic acid in health Physiological effects and mechanisms of action. Ann. Rev. Nutr. 22, 505-531. 

There are at least four known actions of pyridazines on plants involving a one or more of the following effects (a) inhibition of the Hill reaction (photolysis of water during the photosynthesis), (b) inhibition of pigment formation (chlorophylls, carotenoids), (c) change in the linolenic/linoleic acid ratio, and (d) influence on the chloroplast ribosomes. In addition, pyridazines may be used in plant protection as biocides. 

Speculating further on the possible mode of action of linoleic acid, one might assume that the encephalomalacia-producing effect is mediated via... 

The metabolism of CLA in peroxisomes shows interesting aspects in terms of a possible role in the formation and concentration of eicosanoids, especially as effected in different pathologic conditions. By either competing with linoleic acid for desaturation and elongation, or via peroxisomal P-oxidation, CLA may interfere with eicosanoid production and degradation. It is likely however that its action may depend on its incorporation and thereby its concentration in different tissues. The different rate of peroxisomal P-oxidation between t 0,c 2 and c9,tll, may also explain the different biological activities of the two isomers. Also, enhanced fatty acid oxidation... 

Figure 13.13. Effect of dietary linoleic acid on synthesis of active eicosanoids and metabolism. Pathophysiological actions result from faster eicosanoid formation by increased hydroperoxide levels. From Lands etal. (1986).

The perturbation of the incorporation of linoleic add metabolites into mammary gland lipids by CLA metabolism may lead to the hypothesis that CLA is able to create a mild arachidonic acid deficiency condition, in particular in the mammary tissue which is composed mainly of neutral lipids. In fact, because CLA and some of its metabolites are preferentially incorporated into neutral lipids (15), unlike linoleic acid, which is instead incorporated mainly into phospholipids, the preponderance of neutral lipids in the mammary tissue renders the competition between these two fatty acids more favorable toward CLA. It has been demonstrated that mammary tumorigenesis requires essential fatty acids, and eicosanoid inhibitors are able to reduce tumor incidence in experimental models (22). CLA, likely by decreasing the supply of arachidonic acid and inhibiting eicosanoid formation through its metabolites, may counteract arachidonic acid-derived eicosanoid action. Because the decrease of arachidonic acid, CLA metabolite incorporation, TEB density, and tumor incidence correlated with the (XA dietary intake, we can speculate that TEB density could also be modulated by eicosanoids. More data are required, however, to substantiate this hypothesis and to identify which eicosanoid(s) may be responsible for such effects. 

The exact mechanism of action of moisturizers and emollients is still unknown. Theoretically, the improvement in the barrier function could be due to absorption of the moisturizer into the delipidized stratum corneum, acting as an effective barrier, as suggested in a study on the effect of petrolatum (Ghadially et al. 1992). Due to a better knowledge of the structural organization of the horny layer with corneocytes embedded in between lipid bilayers (ceramides, cholesterol and free fatty acids in approximately equal quantities), new emollients could be developed to supply the missing elements in the bilayer structure after acute or chronic irritant contact. However, applications of ceramides, linoleic acid and a variety of other fatty acids alone have been reported to actually delay barrier recovery in acetone-treated murine skin, despite the fact that these lipids are required for barrier homeostasis. The only treatments that allowed normal barrier recovery were applications of complete mixtures of ceramide, fatty acid and cholesterol, or pure cholesterol (Man et al. 

The desaturation of newly synthesized fatty acids apparently proceeds within the plastids or in part also in the cytoplasm. Substituted pyridazinones can have multiple sites of action. Some of them effectively inhibit photosynthetic electron transport and others the carotenoid biosynthesis (Lichtenthaler and Kleudgen 1977).Some of these also block the desaturation of fatty acids. The desaturation of linoleic acid was proposed to be one target (St. John 1976). Treated plants show a higher 18 2/18 3 ratio than untreated plants. Furthermore some pyridazinones inhibit the desaturation of P6 16 0 to PG 16 1 (3-trans) (Khan et al. 1979). Khan proposed that the blocked desaturase may be plastidic, which was proved for Arabidopsis (Norman and St. John, 1987). In general different pyridazinones may act on different desaturases with different l g-values. Another important point is the changed 18 2/18 3 ratio, which may cause a decreased frost-hardening (Fedtke 1982). 

The aim of the present experiment was to study the PDHc activity in the livers and brains of developing rats born to females kept on a fat-free diet from 10 days after mating. The question arises in the mechanism of action of the supplemental linoleic acid given to the progeny after weaning on PDHc activity. Any effect could obviously be either direct, due to variation in the PDHc environment, or could be secondary and due to the stimulation of lipoic acid synthesis needed for further activation of the lipoyl transacetylase and lipoamide dehydrogenase. ... 

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