Dietary (n-3) long-chain PUFA [(n-3) LCPUFA] ameliorate several metabolic risk factors for cardiovascular diseases, although the mechanisms of these beneficial effects are not fully understood. In this study, we compared the effects of dietary (n-3) LCPUFA, in the form of either fish oil (FO) or krill oil (KO) balanced for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, with a control (C) diet containing no EPA and DHA and similar contents of oleic, linoleic, and alpha-linolenic acids, on ectopic fat and inflammation in Zucker rats, a model of obesity and related metabolic dysfunction. Diets were fed for 4 wk. Given the emerging evidence for an association between elevated endocannabinoid concentrations and metabolic syndrome, we also measured tissue endocannabinoid concentrations. In (n-3) LCPUFA-supplemented rats, liver triglycerides and the peritoneal macrophage response to an inflammatory stimulus were significantly lower than in rats fed the control diet, and heart triglycerides were lower, but only in KO-fed rats. These effects were associated with a lower concentration of the endocannabinoids, anandamide and 2-arachidonoylglycerol, in the visceral adipose tissue and of anandamide in the liver and heart, which, in turn, was associated with lower levels of arachidonic acid in membrane phospholipids, but not with higher activity of endocannabinoid-degrading enzymes. Our data suggest that the beneficial effects of a diet enriched with (n-3) LCPUFA are the result of changes in membrane fatty acid composition. The reduction of substrates for inflammatory molecules and endocannabinoids may account for the dampened inflammatory response and the physiological reequilibration of body fat deposition in obese rats.

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Intake of dairy fat has long been considered as a risk factor for CVD. Pasture and dietary lipid supplementation have been reported to be reliable strategies in ruminant nutrition, in order to increase the content of a-linolenic acid (ALA), conjugated linoleic acid (CLA) and vaccenic acid (VA), and decrease SFA in milk fat. In the present study, we aimed at verifying whether consumption of a sheep cheese, naturally enriched in ALA, CLA and VA, would modify the plasma lipid and endocannabinoid profiles in mildly hypercholesterolaemic subjects. A total of forty-two adult volunteers (nineteen males and twenty-three females) with diagnosed mildly hypercholesterolaemia (total cholesterol 5·68 -7·49 mmol/l) were randomly assigned to eat 90 g/d of a control or enriched cheese for 3 weeks, with a cross-over after 3 weeks of washout. Plasma lipids, endocannabinoids, adipokines and inflammatory markers were measured. The intake of enriched cheese significantly increased the plasma concentrations of CLA, VA, the n-3 fatty acids ALA and EPA, and more remarkably decreased that of the endocannabinoid anandamide. LDL-cholesterol decreased significantly (7 %). No changes were detected in the levels of inflammatory markers; however, a significant correlation was found between the plasma levels of anandamide and leptin. The control cheese modified none of the parameters measured. The results obtained do not support the view that intake of dairy fat is detrimental to hypercholesterolaemic subjects. Indeed, they show that a naturally enriched cheese possesses beneficial properties, since it ameliorates the plasma lipid profile, and more remarkably reduces endocannabinoid biosynthesis.

Background. The authors have previously demonstrated in different experimental models that sustained processes of cellular growth are characterized by alterations of cholesterol metabolism not only in the proliferating tissues but also in the plasma compartment. Methods. To evaluate whether alterations of cholesterol metabolism similar to those observed in experimental models are also associated with human cancer, in the present study cholesterol distribution in tumor tissues and lipid composition in the plasma compartment were determined in patients with different types of gastrointestinal cancer. Results. The results showed that tumor tissues contain increased amounts of cholesterol when compared with the corresponding normal tissues. Intracellular alterations of cholesterol were accompanied by specific changes of cholesterol in the plasma compartment: high‐density lipoprotein (HDL) cholesterol was markedly reduced in the serum of patients with gastrointestinal cancer and the lipoprotein profiles showed a decrease in HDL3 fraction, the main HDL subfraction in human serum. The decrease of HDL cholesterol was negatively associated with the clinical stage of the disease. No changes in either total or low‐density lipoprotein cholesterol levels were observed. Conclusions. A major function attributed to HDL is to maintain normal cell cholesterol homeostasis by removing excess of cholesterol from intracellular pools. Because the use and storage of cholesterol are increased within the tumor tissues during growth, it is possible to hypothesize that low HDL levels observed in patients with gastrointestinal cancer are associated with the increased cholesterol metabolism in proliferating tissues.

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BackgroundSeveral evidences suggest that the position of palmitic acid (PA) in dietary triacylglycerol (TAG) influences different biological functions. We aimed at evaluating whether dietary fat with highly enriched (87%) PA in sn-2 position (Hsn-2 PA), by increasing PA incorporation into tissue phospholipids (PL), modifies fatty acid profile and biosynthesis of fatty acid—derived bioactive lipids, such as endocannabinoids and their congeners.Study DesignRats were fed for 5 weeks diets containing Hsn-2 PA or fat with PA randomly distributed in TAG with 18.8% PA in sn-2 position (Lsn-2 PA), and similar total PA concentration. Fatty acid profile in different lipid fractions, endocannabinoids and congeners were measured in intestine, liver, visceral adipose tissue, muscle and brain.ResultsRats on Hsn-2 PA diet had lower levels of anandamide with concomitant increase of its congener palmitoylethanolamide and its precursor PA into visceral adipose tissue phospholipids. In addition, we found an increase of oleoylethanolamide, an avid PPAR alpha ligand, in liver, muscle and brain, associated to higher levels of its precursor oleic acid in liver and muscle, probably derived by elongation and further delta 9 desaturation of PA. Changes in endocannabinoids and congeners were associated to a decrease of circulating TNF alpha after LPS challenge, and to an improved feed efficiency.ConclusionsDietary Hsn-2 PA, by modifying endocannabinoids and congeners biosynthesis in different tissues may potentially concur in the physiological regulation of energy metabolism, brain function and body fat distribution.

Summary The metabolism of cholesterol has been investigated in tumour cells, ascitic fluid and blood serum during the growth of an ascites hepatoma Alterations of cholesterol metabolism have been consistently observed in a variety of experimental tumour models (Coleman & Lavietes, 1981;Van Blitterswijk et al., 1985;Clayman et al., 1986; Erickson et al., 1988) as well as in human neoplasias (Gebhard et al., 1987). These alterations include an increase in cholesterol content, associated with enhanced rates of de novo cholesterol synthesis and deregulation at the level of hydroxy-methyl-glutarylcoenzyme A reductase (HMGR), the rate limiting enzyme in sterol synthesis. It has been suggested that such changes could be related to an increased requirement of cholesterol for new membrane biogenesis that accompany cell growth (Coleman & Lavietes, 1981). More recently, however, the possibility that an increased production of mevalonate and its nonsterol isoprenoid products is needed in the initiating phases of DNA replication has been also proposed (Habenicht et al., 1980;Siperstein, 1984). Similar patterns of intracellular cholesterol metabolism were found in the hepatic hyperplasia induced by a potent mitogen, lead nitrate (Dessi et al., 1984), and in regenerating liver after partial surgical hepatectomy (Dessi et al., 1986). These similarities indicate that the above changes in cholesterol metabolism are related to cell proliferation per se, rather than to tumour growth in particular. Hepatic hyperplasia was characterised by peculiar alterations of cholesterol distribution also in the plasma compartment, namely a decrease in HDL cholesterol as well as in the HDL2/HDL3 ratio (Dessi et al., 1986;.Cholesterol metabolism in the body is regulated through a complex series of transport and biosynthetic mechanisms, which rely on the continuous exchange of cholesterol between tissues and blood. It is thus conceivable that any substantial alteration in the metabolism of cholesterol at the cellular level (e.g. during cell proliferation) may entail changes in the plasmatic pools of cholesterol.In the present study, cholesterol metabolism was investigated in tumour cells and in the blood compartment in rats during the growth of a highly deviated fast growing ascites hepatoma (Yoshida AH-130).The study was made at different time intervals after tumour transplantation in order to evaluate the alterations occurring in the malignant cells and whether these were associated with changes in the cholesterol distribution in the plasma of the host animal, as already observed in different models of cell proliferation (Dessi et al., 1986;