Hypotriglyceridemic effect

Rambjor, G.S., Walen, A.I., Windsor, S.L. and Harris, W.S. (1996) Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans. Lipids. 3LS45-S49. 

In addition to lowering plasma TG, n-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) are reported to have a number of additional beneficial effects on the cardiovascular system which include antihypertensive and antithrombotic actions. EPA and DHA are major fatty acid constituents of fish oil and it has been assumed that both EPA and DHA are responsible for its hypotriglyeeridemic activity. However, growing evidence indicates that EPA and DHA may possess different hypohpidemic properties. We have reported that EPA is the fatty add primarily responsible for the TG-lowering effect of fish oil (Table 1), but the mechanism underlying this hypotriglyceridemic effect has not yet been fully elucidated. Interestingly, however, we... 

In hepatocytes cultured in the presence of oleic acid, incorporation of pH]-water into secreted lipids and TG was lower than incorporation into synthesized lipids with the 3-thia fatty acids. ° A similar phenomenon was observed with pH]-glycerol as the radioactive precursor. This suggests that some of the hypotriglyceridemic effects of 3-thia fatty acids may arise from a reduction in biosynthesis and/or secretion of TG. 

When the synthesis of lipids is reduced due to the presence of fatty acid analogs, the NEFAs will be diverted from the esterification pathway. The level of NEFAs in the hepatocytes treated with 3-thia fatty acids tended to decrease. This indicates that the mitochondrial P-oxidation was increased, as the peroxisomal P-oxidation was unchanged in these hepatocytes. Thus, it is likely that the non-P-oxidizable fatty acid analogs reduced the availability of fatty acids for TG-synthesis due to increased mitochondrial fatty oxidation. The lack of effect on the peroxisomal P-oxidation confirms the in vivo data that the hypotriglyceridemic effect of the analogs can be dissociated from the proliferation of peroxisomes." ... 

Thus, it is likely that rate of TG-synthesis is controlled by coordinate regulation of the activities of mitochondrial P-oxidation and phosphatidate phosphohydrolase. The instant hypotriglyceridemic effect observed in rats given 3-thia fatty acids can be explained by a sudden increase in mitochondrial fatty acid oxidation and a decrease in phosphatidate phosphohydrolase. This alteration is accompanied by a reduction in the... 

Willumsen, N., Skorve, J., Hexebeig, S., Rustan, A.C. Beige, R.K. (1993). Lipids 28 683-689. The hypotriglyceridemic effect of eicosapentaenoic acid in rats is reflected in increased mitochondrial fatty acid oxidation followed by diminished lipogenesis. 

Tetradecylthioacetic acid (TTA) is a fatty acid analogue in which a sulfur atom substitutes the P-methylene group of the alkyl chain. The analogue closely resembles normal fatty acids except that it is unable to be metabolized by P-oxidation. -3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are also poorly oxidized and it has been reported that they inhibit proliferation of cancer cells in culture. Other similarities between TTA and < -3 fatty acids are induction of several enzymes involved in mitochondrial and peroxisomal P-oxidation. Moreover, they have hypotriglyceridemic effects, but TTA is much more potent than EPA. ... 

The viewpoint that the clofibrate effect is entirely through an enhanced peroxisomal p-oxidation has been challenged by Pande and Parvin (1980). These authors point out that the hypotriglyceridemic effect of clofibrate is seen equally in male and female rats although the peroxisomal proliferation is more pronounced in the livers of male rats (Svoboda et aL, 1967). Instead, the authors suggest that, since clofibrate triples the carnitine content of the liver, its effect may be due to enhanced, carnitine dependent, mitochondrial oxidation of fatty acids. 

Wistar rats administered capsaicin (i.p. 3 mg/kg body weight) for three consecutive days showed a reduction of oxidative stress measured as malondialdehyde in the liver, lung, kidney, and muscle [128]. From this study, it is hypothesized that capsaicin can be a potent antioxidant even when consumed for a short period. The influence of capsaicin on the antioxidant status of red blood cells and liver tissue in hyperlipidemic rats is reported [129]. Capsaicin (0.015 %) in the diet which produced the hypotriglyceridemic effect was also effective in reducing the oxidant stress, which was indicated by countering of the depleted antioxidant molecules and antioxidant enzymes in erythrocytes and liver, and decreasing of the elevated lipid peroxide content. The beneficial influence of capsaicin on the antioxidant status of red blood cells and liver in induced hypercholesterolemic rats is also evidenced [130]. The depletion in intracellular thiols and GSH in red blood cells under hypercholesterolemic situation was effectively countered by dietary (0.015 %)... 

Omega-3 fatty acids supplementation may lower blood pressure by their antihypertensive and hypotriglyceridemic effects, and add to the effects of drugs that may also affect blood pressure, such as beta-blockers or diuretics. ... 

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