Effects of saturated and unsaturated fats given with and without dietary cholesterol on hepatic cholesterol synthesis and hepatic lipid metabolism

Hepatic cholesterol synthesis was studied in rats after consuming diets of varying neutral lipid and cholesterol content. Cholesterol synthesis was evaluated by measuring 3-hydroxy-3-methylglutaryl-CoA reductase and by determining the rate of 3H-labeled sterol production from [3H]mevalonate. Results were correlated with sterol balance data and hepatic lipid content. Hepatic cholesterol synthesis was relatively great when cholesterol was excluded from the diet. The source of neutral dietary lipids, saturated vs. unsaturated, produced no change in hepatic sterol synthesis. Values for fecal sterol outputs and hepatic cholesterol levels were also similar in rats consuming either saturated or unsaturated fats. When 1% cholesterol was added to the diet, hepatic cholesterol synthesis was suppressed but the degree of suppression was greater in rats consuming unsaturated vs. saturated fats. This was associated with greater accumulation of cholesterol in livers from rats consuming unsaturates and a reduction in fecal neutral sterol output in this group as opposed to results from rats on saturated fats. Cholesterol consumption also altered the fatty acid composition of hepatic phospholipids producing decreases in the percentages of essential polyunsaturated fatty acids. It is concluded that dietary cholesterol alters cholesterol and fatty acid metabolism in the liver and that this effect is enhanced by dietary unsaturated fats.     

Alteration of the acyl chain composition of free fatty acids,acyl coenzyme A and other liPids by dietary polyunsaturated fats

Dietary alterations were used to demonstrate selective handling of fatty acids during their redistributionin vivo. Differences in the mol Per cent of individual acyl chains in the non-esterified fatty acid, acyl-coenzyme A and PhosPholiPid fractions reflected a result of relative Precursor abundance combined with enzymic selectivities. Selective distributions were observed in the utilization of individual acyl chains between 16:0 and 18:0, 18:1 and 18:2, and among 20:3, 20:4 and 20:5, 22:6 by ligase(s), hydrolase(s) and acyl-transferases. The variations in the mol Per cent of linoleate Present in the acyl-coenzyme A fraction of liver relative to that in the non-esterified fatty acids suggested anin vivo regulation of the level of linoleoyl-coenzyme A that influenced the synthesis of both arachidonoyl-coenzyme A and lipids. The greater abundance of eicosaPentaenoic acid in the free fatty acid fraction relative to that in the acyl-coenzyme A fraction may increase the ability of dietary 20: 5n-3 to be an effective inhibitor of the synthesis of Prostaglandins derived from 20:4n-6.     

A mechanism by which dietary trans fats cause atherosclerosis

Dietary trans fats (TFs) have been causally linked to atherosclerosis, but the mechanism by which they cause the disease remains elusive. Suppressed transforming growth factor (TGF)-β responsiveness in aortic endothelium has been shown to play an important role in the pathogenesis of atherosclerosis in animals with hypercholesterolemia. We investigated the effects of a high TF diet on TGF-β responsiveness in aortic endothelium and integration of cholesterol in tissues. Here, we show that normal mice fed a high TF diet for 24 weeks exhibit atherosclerotic lesions and suppressed TGF-β responsiveness in aortic endothelium. The suppressed TGF-β responsiveness is evidenced by markedly reduced expression of TGF-β type I and II receptors and profoundly decreased levels of phosphorylated Smad2, an important TGF-β response indicator, in aortic endothelium. These mice exhibit greatly increased integration of cholesterol into tissue plasma membranes. These results suggest that dietary TFs cause atherosclerosis, at least in part, by suppressing TGF-β responsiveness. This effect is presumably mediated by the increased deposition of cholesterol into cellular plasma membranes in vascular tissue, as in hypercholesterolemia.     

The effect of dietary pectin on serum lipoprotein cholesterol in rabbits.

The effect of pectin on serum lipoprotein cholesterol during and after induction of hypercholesterolemia in rabbits was studied. The addition of 5% pectin to rabbit diets containing 5% fat and 1% cholesterol partly repressed the rise of serum β- and α-lipoprotein cholesterol. Interestingly, the addition of pectin to the basal diet after the induction of hypercholesterolemia actually delayed the return of serum cholesterol levels to baseline values. Several mechanisms to explain the hypocholesterolemic action of pectin are discussed.     

Regulation of cholesterol metabolism by dietary plant sterols

Renewal has occurred in the use of plant sterols for the treatment of hypercholesterolemias. A novel development was to convert plant sterols to corresponding stanols and esterify them to fat soluble form. In contrast to the crystalline plant sterols or stanols, plant stanol esters can be easily consumed during normal food intake in soluble form in different fat-containing food constituents when they have a potent cholesterol-lowering effect, shown in normo- and hypercholesterolemic men and women without or with coronary heart disease, children and diabetes. Cholesterol lowering is approximately 10% for total and 15% for LDL cholesterol, with the respective values for stanol ester margarine (2-3 g/day stanols) being 15% and 20%. Stanol esters reduce cholesterol absorption efficiency by up to 65%, increase cholesterol elimination in feces as cholesterol itself, usually not as bile acids, and stimulate cholesterol synthesis. Serum beta-carotene level is lowered, but no fat malabsorption or lowering of serum fat soluble vitamins have been observed. In contrast to plant sterols, stanols and their esters are minimally absorbed and they reduce serum plant sterol concentrations, also preventing statin-induced increase of plant sterols. Stanol ester margarine has been included in dietary treatment of hypercholesterolemia followed by the addition of drug treatment in resistant cases.     

Minireview possible roles of dietary fats in carcinogenesis

Epidemiological data have implicated dietary fat as an important factor in the aetiology of various cancers in humans. This suggestion is supported by the results of experiments with animals which have shown that increased amounts of dietary fat, in particular polyunsaturated fat, increase the incidence of some spontaneous and induced tumours. The enhancement of carcinogenesis by dietary fats appears to be exerted at the promotional stage of carcinogenesis. Changes induced by dietary fats in several biological systems involved in carcinogenesis may well indicate the underlying mechanisms responsible for the results of these experiments. These include the effects of dietary fats on the metabolism of chemical carcinogens, the structure and function of membranes, immunocompetence, DNA repair potential and endocrine function.     

Adaptation of the exocrine pancreas to dietary fats

This article reviews studies on the adaptation of the exocrine pancreas to dietary fat. We include all the latest information about the mechanisms that underlie the adaptation of the secretory mechanism of the exocrine pancreas to the amount and the type of dietary fat. We review the kinetics of pancreatic adaptation and the mediators of the adaptive response of the pancreas including cellular and molecular mechanisms (modulation of intracellular messengers and gene expression of the different enzymes and secretagogues involved in the adaptation process). At the same time we include our results in this field in dogs and humans.