Influence of a cod liver oil diet in healthy and insulin-dependent diabetic volunteers on fatty acid pattern, inhibition of prostacyclin formation by low density lipoprotein (LDL) and platelet thromboxane.

Ten healthy and twenty diabetic volunteers (type 1) received 15 capsules (à 450 mg) cod liver oil for 2 weeks daily in addition to a "normal" diet. The levels of eicosapentaenoic acid in the plasma phospholipids of both groups were increased after the treatment. The inhibition of the prostacyclin formation by LDL was diminished when the LDL was isolated after the treatment in comparison to LDL taken in the same concentration and from the same donors before it. The thromboxane B2 (TXB2) synthesis capacity of clotting whole blood, thrombin-induced TXB2 formation by platelets as well as the 15(S)-hydroxy-11 alpha,9 alpha-epoxymethano-5Z, 13E-prostadienoic acid-induced platelet aggregation were not altered by the treatment in healthy volunteers, whereas in diabetics the TXB2 formation capacity of clotting whole blood was decreased after the treatment in comparison with before it.

Negative correlation of eicosapentaenoic acid and lipid accumulation in hepatocytes of diabetics.

In 130 type I and II diabetics with normal serum lipids and in 98 diabetics with type IIa-V hyperlipoproteinemia (HLP), liver biopsies were performed if clinically indicated. During histological examinations of one half of the biopsy specimen lipid droplet size was classified into 4 categories, which were proved by morphometric studies, independent of the amount of fat. From the remaining part the fatty acid composition of triglycerides was analyzed by gas liquid chromatography. Moreover, the fatty acid pattern of serum triglycerides and subcutaneous adipose tissue from the abdominal wall was estimated. The percentage of eicosapentaenoic acid (EPA) in triglycerides of normal diabetic liver (no visible fat) was remarkably high (greater than 30 per cent). In adipose tissue it was low (less than 1 per cent). In serum triglycerides it remained between liver and depot fat (about 3 per cent). EPA decreased with rising lipid droplet size in hepatocytes. Liver diseases, like chronic hepatitis, had no influence on the results. One year after clofibrate treatment, the percentage of EPA in liver appeared increased. In adipose tissue, however, it remained constant. In general, EPA in liver and serum triglycerides was higher in diabetics with normal serum lipids as compared to diabetics with HLP. The decreased availability of EPA in liver and serum triglycerides of diabetics with HLP suggests a significant correlation between this fatty acid and hepatic lipid accumulation which itself is associated with diseases known as risk factors of atherosclerosis.

Influence of a cod liver oil diet in diabetics type I on fatty acid patterns and platelet aggregation.

The influence of an eicosapentaenoic acid rich diet containing only 6,8 g cod liver oil daily for 2 weeks in 20 type I diabetics on fatty acid pattern in serum, platelet aggregation and thiobarbituric acid-reactive substances in serum were studied. There were increases in eicosapentaenoic acid portions in triglycerides, cholesterol esters and phospholipids of serum. This was associated with an inhibition of the platelet hyperaggregation, whereas platelet hyporeactivity is shifted to normal. Hyperreactivity of platelets from diabetics may be caused by enhanced TXA2 formation in comparison to healthy humans (1). On the other hand, diets rich in eicosapentaenoic acid inhibit platelet aggregation in healthy Volunteers (2,3). Therefore we investigated the dietary effect of relatively low doses of cod liver oil in diabetics type I on the eicosapentaenoic acid/arachidonic acid balance.

Thromboxane B2 (TXB2) formation in clotting whole blood of healthy and diabetic humans in vitro.

We investigated the ability of platelets from two groups of diabetics type I and two groups of healthy volunteers matched of age to generate thromboxane B2 (TXB2) during spontaneous clotting of whole blood. The serum concentration of TXB2, reflecting the ability of the platelets to generate TXA2 during clotting, was measured by gas liquid chromatography. Platelets from old diabetics with more than 40 years duration of diabetes mellitus formed significantly less TXB2 than those from old healthy controls. Platelets from juvenile diabetics (9 years duration of disease) formed nearly the same amount of TXB2 as those from young healthy volunteers. The importance of these results is discussed.

[Results of linseed oil and olive oil therapy in hyperlipoproteinemia patients]. / Ergebnisse einer Leinöl- bzw. Olivenöltherapie bei Hyperlipoproteinämie-Patienten.

Only few informations exist on the effect of different oils and the transformation of these precursor fatty acids to prostaglandins in patients with hyperlipoproteinemia. Therefore we investigated the impact of linseed oil and olive oil intake resp. on serum lipoprotein levels, platelet aggregation and fatty acid pattern of serum phospholipids and triglycerides resp. in patients with primary hypercholesterolemia (HC) (n = 13) and hypertriglyceridemia (HTG) (n = 16). The probands were randomly admitted to a 4 week test period with 30 ml olive or linseed oil intake. After linseed or olive oil intake all lipid fractions did not change significantly. Olive oil significantly reduced the platelet aggregation only in patients with HTG, whereas linseed oil failed to influence aggregation. After linseed oil intake there was a significant increase in linolenic and also in eicosapentaenoic acid content of phospholipids in patients with HTG. In contrast to HTG in HC linseed oil only increased significantly the linolenic acid fraction. Our data suggest, that the response of serum lipoproteins, fatty acids and platelet aggregation on modifications in dietary fats depends on the type of lipoprotein disorder.

[Sex-specific differences in food intake, body weight and parameters of lipid metabolism (HDL-cholesterol, total cholesterol and triglycerides) in rats under various feeding conditions]. / Geschlechtsspezifische Unterschiede der Futteraufnahme, des Körpergewichts sowie einiger Parameter des Fettstoffwechsels (HDL-Cholesterol, Gesamtcholesterol, Triglyzeride) bei Ratten unter verschiedenen Fütterungsbedingungen.

We compared the food intake, body weight as well as several parameters of the lipid metabolism in male and female rats fed with a diet high in carbohydrate content (HCD) or high in fat content (HFD). The absolute food intake was higher in male than in female animals. With regard to the relative food intake (per 1 000 g body weight), the sex-specific differences could be demonstrated only in the HCD rats. It was striking that the HFD rats showed the same relative food intake in both sexes but that the females of this group exhibited significantly less weight gain. The HDL-cholesterol serum level was significantly higher in the HFD females than in the males. In the HCD group, we could not find any sex-specific differences. The total cholesterol serum level of female rats was significantly elevated in both diet groups, whereas the triglycerides serum level was only higher in the females of the HCD group, as compared to the corresponding levels of male rats. In the HFD group we could not find any sex-specific differences.

[Fatty acid patterns of triglycerides in serum and skeletal muscles of rabbits on a cholesterol diet]. / Fettsäuremuster der Triglyzeride des Serums und Skelettmuskels bei Kaninchen mit Cholesteroldiät.

In 18 rabbits a hypercholesterolaemia was produced by a 12-week dietetic load with cholesterol. The hypercholesterolaemic rabbits had increased proportions of saturated and simply unsaturated fatty acids in the triglycerides of the serum and the skeletal muscle. The content of eicosapentaenic acid was lowered. The alterations in the fatty acid pattern are equal to those of patients with hyperlipoproteinaemia and arteriosclerosis. On the basis of these findings rabbits seems to be a suitable model, in order to investigate the connections between fatty acid patterns and the development of arteriosclerosis by experiments on animals.

[Fatty acid composition of triglycerides in inflammatory liver diseases in diabetics with and without hyperlipoproteinemia]. / Zum Fettsäurenmuster der Triglyzeride bei entzündlichen Lebererkrankungen von Diabetikern ohne und mit hyperlipoproteinämie.

In 228 patients with diabetes mellitus (130 diabetics without and 98 diabetics with hyperlipoproteinaemia) percutaneous liver punctures after Menghini as well as biopsies of the subcutaneous fatty tissue were carried out. From the biopsy specimens and from serum the fatty acid pattern of triglycerides was estimated. In 87 patients with chronic aggressive hepatitis and 37 patients with fibrosis no differences in the fatty acid composition could be found. According to the present findings there was no evidence of alterations in the supply of individual fatty acids caused by chronic hepatitis per se. However, it is to be taken into consideration that simultaneous liver steatosis can provoke marked changes in the fatty acid pattern of liver triglycerides. The best reference seems to be the size of the fat droplet in the hepatocytes. Its rise is associated with an increase of palmitic and oleic acid, whereas the percentage of arachidonic and eicosapentaenoic acid is decreased. It must be clarified by further studies, whether this reveals a general pathophysiological phenomenon or is restricted to diabetic subjects.

Decrease of eicosapentaenoic acid in fatty liver of diabetic subjects.

Simultaneous biopsies of liver and subcutaneous adipose tissue have been carried out in 228 patients with diabetes mellitus. In liver triglycerides a marked variability of the fatty acid pattern in relation to fatty degeneration of liver parenchyma has been confirmed. In adipose tissue fatty acid pattern was relatively constant. The most striking finding was a high content of eicosapentaenoic acid in normal liver and its decrease with the rise of lipid droplet size in the hepatocytes. No correlation with the quantity of liver fat or inflammatory liver diseases could be ascertained. When diabetes was associated with hyperlipoproteinemia (HLP) the percentage of eicosapentaenoic acid was significantly less. From the results the suggestion is obvious that a diminution of eicosapentaenoic acid in hepatic triglycerides is associated with lipid accumulation in the liver cells. A local mechanism, possibly the antilipolytic potency of prostaglandins, may be responsible for the creation of lipid droplets in liver cells of patients with metabolic disturbances. The alterations of eicosapentaenoic acid should be considered in view of recent data on the antiaggregatory effect of this fatty acid and its possibly preventive role for atherosclerosis.

The triglyceride fatty acid pattern in arterial wall, adipose tissue and serum of amputated diabetic subjects.

The triglyceride fatty acid pattern [TFAP] in arterial wall, adipose tissue and serum has been estimated in diabetic subjects by gas-liquid chromatography simultaneously. The samples were taken shortly before or during femoral amputation performed under halothane anaesthesia. In addition, in some probands the fatty acids of cholesterol esters of vascular walls have been obtained. The following differences in the TFAP of the tissues under study were discovered. In arterial wall compared to serum, lauric, myristic, myristoleic, palmitoleic, stearic, oleic and linolenic acid were increased; palmitic and linoleic acid were decreased, whereas eicosatrienoic, arachidonic and eicosapentaenoic acid were at the same level. In arterial wall compared to adipose tissue, myristic, palmitic and nervonic acid were decreased; eicosatrienoic, arachidonic and eicosapentaenoic acid were increased. Most differences concern the TFAP of adipose tissue compared to serum: lauric, myristic, myristoleic, palmitoleic, oleic, linolenic, lignoceric and nervonic acid were elevated in the former; palmitic, linoleic, eicosatrienoic, arachidonic and eicosapentaenoic acid were increased in the latter. In consideration of different content of fatty acids in the tissues studied the authors conclude that certain fatty acids have distinct metabolic positions such as depot fatty acids and precursors of prostaglandins.

The fatty acid pattern of triglycerides in liver, adipose tissue and serum of diabetics with hyperlipoproteinemia before and during clofibrate treatment.

In 20 diabetic inpatients with type IIb, III, IV and V hyperlipoproteinemia (HPL) the triglyceride fatty acid pattern (TFAP) of serum, adipose tissue and liver biopsy specimens before and after one year of clofibrate treatment has been determined by gas-liquid chromatography. Compared to previous results which revealed a correlation between fat droplet size and the TFAP in liver parenchyma cells, remarkable changes were observed after long-term therapy. In adipose tissue, only linoleic acid increased significantly from 8.6 to 11.3%. In serum, myristic and palmitic acid decreased, whereas linoleic, eicosatetraenoic (arachidonic) and eicosapentaenoic acid rose significantly. In liver fat, palmitic acid decreased, whereas linoleic, eicosatrienoic, arachidonic and eicosapentaenoic acid significantly increased. After clofibrate therapy, the TFAP in diabetic subjects with HLP became similar to that of diabetics without HLP. The most pronounced changes were found in the liver, serum having an intermediate position between liver and adipose tissue. The pathophysiological relevance in view of possible relations to prostaglandins has been discussed.

The fatty acid composition of triglycerides in arteries, depot fat and serum of amputated diabetics.

The triglyceride fatty acid pattern (TFAP) in arterial wall, adipose tissue and serum in vivo has been estimated in amputated diabetic subjects by gas-liquid chromatography simultaneously. Besides, in some probands the fatty acid pattern of cholesterol esters of vessel walls has been obtained. In arterial wall the percental content of lauric, myristic, myristoleic, palmitoleic, stearic, oleic and linolenic acid was high and that of palmitic and linoleic acid was low, when compared to serum, whereas eicosatrienoic, arachidonic and eicosapentaenoic acid were of similar magnitude. In comparison to adipose tissue myristic, palmitic and nervonic acid were decreased and eicosatrienoic, arachidonic and eicosapentaenoic acid were increased in arterial wall. In view of the results the speculation is obvious that certain fatty acids have distinct metabolic positions in several tissues, such as depot fatty acids and precursors of prostaglandins, for example.