Adaptation to chronic ethanol administration emphasized by fatty acid hydroxylations in rat liver and kidney microsomes

BACKGROUND: Long-term ethanol consumption in laboratory animals is associated with histological alterations of liver cells and modifications of fatty acid metabolism. AIM OF THE STUDY: The present study was aimed at investigating the effect of 1- and 2-month chronic treatment of rats with ethanol on the metabolism of two unsaturated (oleic and linoleic) fatty acids in liver and kidney microsomes, in relation to the CYP2E1 enzyme content in both tissues. METHODS: Rats were fed ethanol (14 g/Kg/d) or dextrose through a permanently implanted gastric cannula, as described in the intragastric feeding rat model for alcoholic liver disease (ALD). CYP2E1 level was immuno-quantified in both liver and kidney microsomes by Western blot, whereas fatty acid omega- and (omega-1)-hydroxylations were measured using HPLC and radiometric analytical methods. RESULTS: One- and two-month ethanol treatment led to a 3- to 4-fold rise of the CYP2E1 protein in both liver and kidney microsomes. Oleic and linoleic acid (omega-1)-hydroxylations were increased (approximately 3-fold) in liver microsomes after one-month of ethanol administration, but surprisingly such a rise was not observed after a two-month treatment; on the other hand, no effect was observed on the omega-hydroxylations of these fatty acids. Furthermore, as previously described for lauric acid, ethanol intake did not significantly act on the kidney microsome capability to hydroxylate unsaturated fatty acids. CONCLUSIONS: CYP2E1 is strongly inducible by ethanol and therefore accounts for the tolerance for this hepatotoxicant. Our results support the development of an adaptation process in the liver hydroxylating enzyme system, which occurs between one and two months of ethanol feeding. Although it is usually not appropriate to extrapolate animal findings to humans, rat and human CYP2E1s were observed to have comparable specificities and similar mechanisms of regulation. Thus, the present study allowed the acquirement of detailed information of CYP2E1 activity in patients with severe manifestations of ALD.     

Effects of Japanese torreya (Torreya nucifera) seed oil on lipid metabolism in rats

OBJECTIVE: We investigated effects of Japanese torreya (Torreya nucifera) seed oil containing non-methylene-interrupted polyunsaturated fatty acid of all-cis-5,11,14-eicosatrienoic acid (sciadonic acid) on rat lipid metabolism. METHODS: Male Sprague-Dawley rats were fed the experimental diets based on AIN-93 containing 10% corn, soybean, or torreya oil for 4 wk. Blood and tissues were recovered from each rat, and concentrations of triacylglycerol, cholesterol, and phospholipid in plasma and liver were determined by enzymatic assays. Moreover, fatty acid composition was analyzed for triacylglycerol, cholesterol ester, and phospholipid isolated from plasma and liver lipids by gas liquid chromatography. RESULTS: Plasma triacylglycerol level in rats fed torreya oil was lower than that in rats fed corn or soybean oil, although there were no significant differences in plasma cholesterol and phospholipid levels in all rats. Liver triacylglycerol level was also lower in rats fed torreya oil, whereas liver cholesterol and phospholipid levers were same for all rats. omega-3 Polyunsaturated fatty acids such as 22:6 (omega-3) were lower in plasma and liver lipids of torreya and corn oil groups, whereas omega-6 polyunsaturated fatty acids such as 22:4 (omega-6) and 22:5 (omega-6) were higher. Considerable amounts of sciadonic acid were detected in cholesterol ester, triacylglycerol, and phospholipid in plasma and liver of rats fed torreya oil. CONCLUSION: These observations suggest that torreya seed oil can modify lipid metabolism, resulting in lower triacylglycerol levels in plasma and liver of rats.     

Dietary fish protein lowers blood pressure and alters tissue polyunsaturated fatty acid composition in spontaneously hypertensive rats

OBJECTIVE: To investigate the effect of two types of dietary protein on blood pressure, liver fatty acid desaturation and composition, and urine 6-keto-prostaglandin-F (PGF(1alpha)) level, the metabolite of prostacyclin. METHODS: 5-wk-old spontaneously hypertensive rats were fed 20% casein or purified fish protein. The fat source was 5% ISIO oil, which contains 47.9% (omega-6) and 1.7% (omega-3) total polyunsaturated fatty acids. After 2 mo on the diet, systolic blood pressure was reduced with fish protein compared with casein (189.8 +/- 10.5 versus 220.7 +/- 8.7). RESULTS: Excretion of 6-keto-PGF(1alpha) in urine was negatively correlated with blood pressure. Liver cholesterol and phospholipid concentrations were 1.71- and 1.27-fold lower with fish protein than with casein, respectively. The fish protein diet lowered the 20:4(omega-6) proportion and the ratio of 20:4(omega-6) to 18:2(omega-6) in liver microsomal lipids and phospholipids, which was due to the reduced microsomal Delta6(omega-6) desaturation activity. Dietary protein source did not affect omega-3 fatty acid composition, and this was associated with a similar activation of Delta6(omega-3) desaturation in liver microsomes. CONCLUSIONS: The present data indicated a significant blood pressure-lowering effect caused by fish protein, rather than by casein, that modified the fatty acid composition of liver phospholipids and liver microsomal total lipids.     

Diets rich in polyunsaturated fatty acids: effect on hepatic metabolism in rats

OBJECTIVE: We investigated the effect of diets rich in omega-6 and omega-3 fatty acids on hepatic metabolism. METHODS: Male Wistar rats, just weaned, were fed ad libitum for 8 wk with one of the following diets: rat chow (C), rat chow containing 15% (w/w) soybean oil (S), rat chow containing 15% (w/w) fish oil (F), and rat chow containing 15% soy bean and fish oil (SF; 5:1, w/w). Casein was added to the fatty diets to achieve the same content of protein (20%) as the control chow. The rats were killed by decapitation, and the hepatic tissue was removed and weighed. Tissue lipid, glycogen, and protein content, in vivo lipogenesis rate, and adenosine triphosphate citrate lyase and malic enzyme activities were evaluated. Plasma total lipids, triacylglycerol, and cholesterol concentrations were assessed. RESULTS: Body weight gain was higher in F and SF than in C and S rats. Liver weight, lipid content, and lipogenesis rate increased in F and SF rats, although adenosine triphosphate citrate lyase activity decreased. Glycogen concentration decreased in S, F, and SF rats compared with C rats. Plasma total lipids and triacylglycerol concentrations were lower in F and SF than in C rats. Total and high-density lipoprotein cholesterol (HDL-C) plasma levels decreased in F rats, with maintenance of the total:HDL-C ratio. In SF rats, an increase in HDL-C led to a lower total:HDL-C ratio. CONCLUSIONS: These results indicated that an enrichment of the diet with omega-3 polyunsaturated fatty acids produces hypolipidemia but may cause changes in liver metabolism that favor lipid deposition. They also suggested that the addition of a small amount of eicosapentaenoic and docosahexaenoic polyunsaturated fatty acids to an omega-6-rich diet further improve the circulating lipid profile, in comparison with an omega-3-rich diet, but it does not prevent excess liver lipid accumulation.     

Some novel insights into the pathogenesis of alcoholic steatosis.

The pathogenesis of alcoholic steatosis is a complex process that is manifested through several mechanisms involving some of or all the following body metabolism components: increased fat synthesis, increased mobilization of depot fat, defective export of fat from the liver, and decreased fat breakdown. Some of the novel findings in these mechanisms involve the down-regulation of peroxisome proliferator-activated receptor alpha and up-regulation of lipogenic enzymes through the induction of sterol regulatory element-binding protein. Yet another mechanism that remains viable is the adenosine 5'-monophosphate-activated protein kinase, which, through a complex mechanism, may regulate the relative concentrations of intracellular malonyl coenzyme A and long-chain acyl-coenzyme A, the key metabolites responsible for the balance between fat synthesis versus degradation pathways. Finally, excess dietary intake of omega-6 polyunsaturated fatty acids may exacerbate alcohol-induced onset of hepatic steatosis and alcoholic liver disease. This may explain why supplementation with lecithin containing omega-6 polyunsaturated fatty acids in a recent clinical trial in human beings failed to show any beneficial effects, although it was partially effective in an animal model. In contrast, dietary intake of omega-3 polyunsaturated fatty acids in moderation may have a protective effect against steatosis and alcoholic liver disease.     

Dietary effect of omega-3 type polyunsaturated fatty acids on serum and liver lipid levels in rats

The dietary effect of omega-3 type highly polyunsaturated fatty acid concentrate (PUFA mix) was investigated on cholesterol and triglyceride levels in the serum and liver, and high density lipoprotein cholesterol (HDL-cholesterol) levels in the serum. The PUFA mix prepared from squid liver oil contained about 75% of total omega-3 type fatty acids. In rats fed the normal diet to which 3% PUFA mix was added, the levels of triglyceride, total cholesterol and phospholipid in the serum markedly decreased as compared to rats fed a 3% methyl-oleate diet. However, lipid peroxide values in the liver and serum increased in rats fed PUFA mix-diets. In the hypercholesterolemic rats, a 5% PUFA mix-diet caused growth retardation and a corresponding reduction in food intake. Lipid peroxide in the liver and serum were more elevated in rats fed diets containing 1, 3 and 5% PUFA mix than in rats fed diets containing 5% oleate or 5% linoleate. In all the rats on PUFA mix-diets, there were depression of serum total cholesterol and elevation of serum HDL-cholesterol. The ratio of HDL-cholesterol to total cholesterol increased in proportion to the amounts of dietary PUFA mix. Total cholesterol level in the liver was depressed after PUFA mix feeding.     

An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.     

Lipid metabolism during the perinatal phase, and its implications on postnatal development

During pregnancy, lipid metabolism plays a major role to warrant the availability of substrates to the foetus. By using different experimental designs in the rat we have been able to answer several questions that were open about the short- and long-term effects of alterations of lipid metabolism during the perinatal stage. The first one was to demonstrate the importance of maternal body fat depot accumulation during the first half of pregnancy. We found that conditions like undernutrition circumscribed to this specific period when foetal growth is still small, that impede such fat accumulation not only restrain intrauterine development but also have long-term consequences, as shown by an impaired glucose tolerance when adults. Secondly, undernutrition during suckling has major long-term effect decreasing body weight, even though food intake was kept normal from the weaning period. Present findings also show that a diet rich in omega-3 fatty acids during pregnancy and lactation has negative effects on offspring development, but cross fostered experiments showed that the effect was a consequence of the intake of these fatty acids during the lactation period rather than during pregnancy. Pups from dams that were fed a fish oil-rich diet during pregnancy and lactation were found to have altered glucose/insulin relationship at the age of 10 weeks. Since a omega-3 fatty acid-rich diet decreases milk yield during lactation, additional experiments were carried out to determine whether decreased food intake, altered dietary fatty acid composition, or both were responsible for the long-term effects on the glucose/insulin axis. Results show that the decreased food intake caused by a omega-3 fatty acid-rich diet rather than the change in milk composition during suckling was responsible for the reduced pancreatic glucose responsiveness to insulin release at 16 weeks of age. In conclusion, present findings indicate that impaired maternal fat accumulation during early pregnancy and food intake during lactation, rather than a difference in dietary fatty acid composition have a greater influence on postnatal development and affect glucose/insulin relationships in adult rats.     

Metabolic aspects of trans fatty acids

The consumption of trans isomers of unsaturated fatty acids has been associated withuntoward metabolic effects. Several clinical investigations demonstrated that trans fatty acids increase plasma LDL-cholesterol and lipoprotein (a) and reduce HDL-cholesterol concentrations. These alterations of plasma lipid profiles indicate an atherogenic effect of trans fatty acids. Both in preterm infants and in healthy children aged 1-15 years, we found blood plasma arachidonic acid (C20:4omega-6) levels and the product/substrate ratios of arachidonic acid synthesis (C20:4omega-6/C18:2omega-6) inversely correlated to the level of the principal trans fatty acid, trans octadecaenoic acid (C18:1omega-9/7, trans), which is compatible with a dose-dependent inhibition of arachidonic acid synthesis by trans fatty acids. Moreover, in premature infants trans fatty acids in blood plasma correlated inversely with birth weight in an observational study, indicating that trans fatty acids may impair early human growth. It appears desirable to limit the dietary intake of trans fatty acids. The major dietary sources of trans fatty acids are partially hydrogenated vegetable and fish oils. Refinement of the industrial technology of partial hydrogenation and appropriate food labelling may lead to a considerably decrease of human exposure to trans fatty acids.     

The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease

A high omega-6/omega-3 ratio, as is found in today's Western diets, promotes the pathogenesis of many chronic diseases, including cardiovascular disease. Increased dietary intake of linoleic acid (LA) leads to oxidation of low-density lipoprotein (LDL), platelet aggregation, and interferes with the incorporation of essential fatty acids (EFA) in cell membrane phopholipids. Both omega-6 and omega-3 fatty acids influence gene expression. Omega-3 fatty acids have strong anti-inflammatory effects, suppress interleukin 1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6), whereas omega-6 fatty acids tend to be pro-inflammatory. Because inflammation is at the base of many chronic diseases, including coronary heart disease, dietary intake of omega-3 fatty acids plays an important role in the manifestation of disease, particularly in persons with genetic variation, as for example in individuals with genetic variants at the 5-lipoxygenase (5-LO). Increased dietary arachidonic acid (AA) significantly enhances the apparent atherogenic effect of genotype, whereas increased dietary intake of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) blunts this effect. The diet-gene interaction further suggests that dietary omega-6 fatty acids promote, whereas marine omega-3 fatty acids EPA and DHA inhibit leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation.     

Dietary eritadenine and ethanolamine depress fatty acid desaturase activities by increasing liver microsomal phosphatidylethanolamine in rats

The effects of eritadenine, a constituent of the Lentinus edodes mushroom, and ethanolamine, the base constituent of phosphatidylethanolamine (PE), on fatty acid desaturase activities and lipid profiles were investigated comparatively in rats. Rats were fed a control diet or a diet supplemented with either eritadenine (0.05 g/kg) or ethanolamine (8 g/kg) for 14 d. Eritadenine and ethanolamine had marked hypocholesterolemic effects. The concentration of liver microsomal PE was significantly increased and the ratio of phosphatidylcholine (PC) to PE was significantly decreased by both eritadenine and ethanolamine. These changes in phospholipid profile were also observed in the mitochondria and plasma membranes in the liver. The activities of the Delta5-, Delta6- and Delta9-desaturases in liver microsomes were significantly decreased by eritadenine and ethanolamine; there was a significant correlation between the activity of Delta5- or Delta6-desaturase and the proportion of PE in the total phospholipids or the PC/PE ratio. Reflecting decreased Delta5- and Delta6-desaturase activities, the 20:4(n-6)/18:2(n-6) ratio was significantly decreased by eritadenine and ethanolamine in PC of the liver microsomes, mitochondria and plasma membranes. Although the 20:4(n-6)/18:2(n-6) ratio of liver microsomal PE was also significantly decreased by eritadenine and ethanolamine, the fatty acid composition of phosphatidylinositol and phosphatidylserine was less affected by these compounds. Eritadenine and ethanolamine increased the proportion of 16:0-18:2 and decreased the proportion of 18:0-20:4 in liver PC. The results suggest that dietary eritadenine and ethanolamine might lead to decreases in desaturase activities and changes in fatty acid and molecular species composition of PC through an increase in liver microsomal PE.     

Monounsaturated and omega-3 but not omega-6 polyunsaturated fatty acids improve hepatic fibrosis in hypercholesterolemic rabbits

OBJECTIVE: Although the influence of saturated fatty acids, monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), lipids, cholesterol levels, and other blood lipids has been established, few studies have examined the influence of these dietary lipids on the composition and histologic damage of organs in situations of hypercholesterolemia. Biliary lipids come from the liver, and this organ is essential in cholesterol homeostasis; thus, it may be helpful to evaluate the inter-relations among biliary, hepatic lipids, and hepatotoxic effects in situations of hypercholesterolemia with different dietary lipids. This study investigated whether administration of diets differing in fatty acid profiles (omega-3 PUFA, omega-6 PUFA, or MUFA) influence the content of biliary lipids, the lithogenic index of gallbladder bile, and the development of hepatic fibrosis in hypercholesterolemic rabbits. METHODS: Thirty rabbits were randomized to one of five groups. A control group received rabbit chow for 80 d. The remaining four groups received a 50-d diet that contained 3% lard and 13% cholesterol to provoke hypercholesterolemia. After this period, three groups were fed for another 30 d on a diet enriched with omega-6 PUFAs, MUFAs, and omega-3 PUFAs, respectively. Liver, bile, and plasma lipid compositions, lipid peroxidation in hepatic mitochondria, and histologic hepatic lesions were analyzed. RESULTS AND CONCLUSIONS: There was a beneficial effect of MUFA and omega-3 PUFA on hepatic fibrosis in hypercholesterolemic rabbits because both dietary fats led to recovery from hepatic lesions. However, because intake of omega-3 PUFA provoked lithogenic bile in rabbits, MUFA intake would be more advisable.     

Beneficial effects of omega-3 fatty acids on the consequences of a fructose diet are not mediated by PPAR delta or PGC1 alpha

Purpose

To study, in high-fructose-fed rats, the effect of a dietary enrichment in omega-3 polyunsaturated fatty acids (n-3 PUFA) on the expression of genes involved in lipid metabolism and cardiovascular function.

Methods

Twenty-eight male “Wistar Han” rats received for 8 weeks, either a standard chow food or an isocaloric 67 % fructose diet enriched or not in alpha-linolenic acid (ALA) or in docosahexaenoic (DHA) and eicosapentaenoic acids (EPA) mix (DHA/EPA). After sacrifice, blood was withdrawn for biochemical analyses; heart, periepididymal adipose tissue and liver were collected and analyzed for the expression of 22 genes by real-time PCR.

Results

Fructose intake resulted in an increase in liver weight and triglyceride content, plasma triglyceride and cholesterol concentrations, although no difference in glucose and insulin. In the liver, lipogenesis was promoted as illustrated by an increase in stearoyl-CoA desaturase and fatty acid synthase (Fasn) together with a decrease in PPAR gamma, delta and PPAR gamma coactivator 1 alpha (PGC1 alpha) expression. In the heart, Fasn and PPAR delta expression were increased. The addition of ALA or DHA/EPA into the diet resulted in a protection against fructose effects except for the decreased expression of PPARs in the liver that was not counterbalanced by n-3 PUFA suggesting that n-3 PUFA and fructose act independently on the expression of PPARs and PGC1 alpha.

Conclusions

In liver, but not in heart, the fructose-enriched diet induces an early tissue-specific reduction in PPAR gamma and delta expression, which is insensitive to n-3 PUFA intake and dissociated from lipogenesis.     

Dietary 5-campestenone (campest-5-en-3-one) enhances fatty acid oxidation in perfused rat liver

The effect of dietary 5-campestenone (campest-5-en-3-one), a chemical modification product of a naturally-occurring plant sterol, campesterol, on lipid metabolism was examined using a rat liver perfusion system. Male Sprague-Dawley rats weighing about 140 g were fed a diet supplemented with or without 0.2% 5-campestenone for 14 d. 5-Campestenone feeding resulted in a marked reduction in the concentrations of serum lipids, such as triacylglycerol (TG), cholesterol, phospholipid, and free fatty acid, without influencing food intake or growth. Then, isolated livers from both groups were perfused for 4 h in the presence of an exogenous linoelaidic acid substrate. Dietary 5-campestenone markedly elevated hepatic ketone body production, while cumulative secretions of TG, cholesterol, and phospholipid by the livers of rats fed 5-campestenone were all significantly lowered as compared to those fed without the compound: the extent of the reduction was more prominent in the secretion of TG than other lipid components. In addition, the reduction of TG secretion was concomitantly accompanied by the reduced incorporation of both exogenous and endogenous fatty acids into this lipid molecule. These results suggest that dietary 5-campestenone exerts its hypotriglyceridemic effect, at least, in part through an enhanced metabolism of endogenous and exogenous fatty acids to oxidation at the expense of esterification in rat liver.     

Prevention of chemically induced diabetes mellitus in experimental animals by polyunsaturated fatty acids

Previous studies showed that essential fatty-acid deficiency, conjugated linoleic acid, and a peroxisome proliferator-activated receptor-gamma binding agent such as troglitazone can prevent the development of diabetes mellitus in experimental animals. In the present study, we observed that oral supplementation with oils rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid could protect the animals against alloxan-induced diabetes mellitus. These oils rich in omega-3 and omega-6 fatty acids not only significantly attenuated chemical-induced diabetes mellitus but also restored the antioxidant status to normal range. Changes in the concentrations of different fatty acids shown by the phospholipid fractions of plasma, liver, and muscle tissues that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in these animals. Based on these results and the known mechanisms of alloxan, we suggest that omega-3 and omega-6 long-chain fatty acids can prevent chemically induced diabetes mellitus by enhancing the antioxidant status and suppressing production of cytokines.     

Effect of reduced dietary protein intake on hepatic and plasma essential fatty acid concentrations in the adult female rat: effect of pregnancy and consequences for accumulation of arachidonic and docosahexaenoic acids in fetal liver and brain

During pregnancy, the accumulation of long-chain polyunsaturated fatty acids (LCPUFA) in fetal tissues places a substantial demand upon maternal lipid metabolism. As lipid metabolism is intimately linked to aspects of protein metabolism, a reduced protein intake in pregnancy may impair activities of enzymes and transport proteins responsible for supplying LCPUFA to the fetus, thereby compromising fetal development. We have investigated the effect of reduced protein intake on LCPUFA status in the non-pregnant rat and in the pregnant rat, and in fetus at day 20 of gestation. Female rats (n 5 per group) were either mated and fed the control diet (180 g protein/kg) or low-protein diet (90 g protein/kg, LPD) diet throughout pregnancy, or fed the control diet or LPD for 20 d (non-pregnant animals). The fatty acid compositions of maternal liver and plasma, and fetal liver and brain were determined by GC. Feeding the LPD did not lead to any gross changes either in adult or fetal growth, or in total lipid concentrations in adult rat liver. However, the LPD was associated specifically with lower liver (42.6 %) and plasma (19.4 %) phosphatidylcholine (PC), and plasma triacylglycerol (28.6 %) docosahexaenoic acid (DHA) concentrations in pregnant rats and reduced fetal brain PC- (26.1 %) and phosphatidylethanolamine- (25.6 %) DHA concentrations. Together, these results show that variations in maternal dietary protein consumption alter DHA status in pregnancy and modify DHA accumulation into the fetal brain. The present results suggest that lower maternal protein intakes reduce delivery of DHA from the mother to the fetus, which may impair development and function of the fetal brain.     

Beneficial Outcomes of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on Human Health: An Update for 2021

Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose–response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.