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Piccinin, E. Oleic Acid in Gut-Liver Axis. Encyclopedia. Available online: (accessed on 07 December 2023).
Piccinin E. Oleic Acid in Gut-Liver Axis. Encyclopedia. Available at: Accessed December 07, 2023.
Piccinin, Elena. "Oleic Acid in Gut-Liver Axis" Encyclopedia, (accessed December 07, 2023).
Piccinin, E.(2021, August 30). Oleic Acid in Gut-Liver Axis. In Encyclopedia.
Piccinin, Elena. "Oleic Acid in Gut-Liver Axis." Encyclopedia. Web. 30 August, 2021.
Oleic Acid in Gut-Liver Axis

Oleic acid is not an essential fatty acid since it can be endogenously synthesized in humans. Stearoyl-CoA desaturase 1 (SCD1) is the enzyme responsible for oleic acid production and, more generally, for the synthesis of monounsaturated fatty acids (MUFA). The saturated to monounsaturated fatty acid ratio affects the regulation of cell growth and differentiation, and alteration in this ratio has been implicated in a variety of diseases, such as liver dysfunction and intestinal inflammation. 

olive oil oleic acid MUFA stearoyl-CoA desaturase liver gut

1. Introduction

Dietary recommendations suggest that fat should represent 20% to 35% of energy intake and the type of fat ingested is a fundamental clue in the prevention of several diseases [1]. Indeed, fat overconsumption and fat quality have been linked to obesity, insulin resistance and the metabolic syndrome [2]. Dietary fats and oils are composed of triglycerides made of three fatty acids esterified on a glycerol backbone. As fatty acids are highly diverse, the classifications of fatty acids are based on their carbon chain length, the number and the position of the unsaturations (double bounds) present between two carbons. They are classified into different families: saturated FA (SFA), with no unsaturation such as palmitic or stearic acids, monounsaturated (MUFA)—if it contains one double bond—and polyunsaturated (PUFA)—if there are more than one. The palmitoleic acid (16:1) and the oleic acid (18:1) represent two important MUFA. The PUFAs can further be subdivided into the two renowned omega-6 (n-6) (linoleic acid, arachidonic acid) and omega-3 (n-3) acids (α-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)) based on the distance from the first double bond to the methyl end, although PUFA n-7 and n-9 exist [3]. Both omega-6 and omega-3 are essential fatty acids and must be obtained exclusively from the dietary sources.
According to conventional dietary recommendations, a healthy diet should include a daily consumption of fats: an inadequate quantity of fat might increase the risk of conditions such as depression, psoriasis, Alzheimer’s disease and schizophrenia [4][5]. To date, several edible oils have been characterized for their health benefits, particularly due to their abundance in MUFA and/or PUFA. Extra-virgin olive oil (EVOO), sunflower oil (SFO), palm oil, and fish oil have been extensively studied for their contribution to disease prevention. However, other types of edible oils may play a role in preserving health status. For instance, due to their high concentration in MUFA and PUFA and a low quantity of SFA, mustard and canola oils display beneficial effects on lipid serum profile and the cardiovascular system [6][7].
EVOO represents the main source of fat in the Mediterranean diet [8]. It is constituted by a high content of MUFA (mostly oleic acid), a variable but significant amount of PUFA (ranging from 1.5% to 21%), and minor amounts of antioxidant micronutrients such as polyphenols, squalene, lignans, phenyl-ethyl alcohols and secoiridoids [9][10]. Oleic acid (18:1 n-9) represents 49% to 83% of total FA in olive oil [11] and its consumption has been related to improved pancreas and liver secretory activity as well as reduced gastric-duodenal ulcers risk [12]. Moreover, MUFAs are able to modify plasma lipids and lipoprotein composition and hence reduce inflammation, oxidative stress and coagulation and ameliorate glucose homeostasis and blood pressure [12]. This evidence has confirmed the beneficial properties of EVOO bioactive components that have led to the established health claims by FDA and EFSA. Both agencies stated that oleic acid contained in olive oil, together with the present polyphenols, contributes to the maintenance of normal blood cholesterol levels [13][14].
The SFO contains a large amount of PUFA (linoleic acid 60% to 70%), but MUFA (oleic acid), SFA (stearic acid) and tocopherol are present as well in adequate quantities [15][16]. This oil has traditionally been used as control in several studies [15][17]. It has been shown that SFO can modify the serum lipid profile by reducing total cholesterol and low-density lipoprotein (LDL) levels [18][19]. On the other hand, a diet rich in linoleic acid increases reactive oxygen species (ROS) production compared to a SFA-rich diet, thereby promoting lipid peroxidation [2].
Different from the previous two fatty acids, fish oil is a good source of the B12 and D vitamins and omega-3 FAs (EPA and DHA) [20][21]. The favourable health effects of fish oil were initially established by the remarkably low incidence of coronary artery disease within the Inuit community, despite consuming a high-fat diet [22]. These health effects have largely been attributed to EPA and DHA. Indeed, several studies have reported that diet supplementation with purified EPA and DHA for more than three years result in cardioprotective effects [23][24]. In the past years, several meta-analyses and systematic reviews have been published in order to evaluate the association between fish oil and protection from cardiovascular risk [25][26][27][28][29][30][31][32]. Most of the studies reported no significant association of omega-3 supplementation with fatal or nonfatal coronary heart disease or any major vascular events. Furthermore, a large cohort study recently demonstrated that diet supplemented with fish oil containing omega-3 failed to reduce the incidence of major cardiovascular events or cancer [33]. If omega-3 FA supplement containing EPA and DHA is approved from FDA, it is not the same for the other dietary supplements of fish oil. Different from the first, fish oil supplement can include other fats and cholesterols as well, which may negatively affect the health response [34].
Palm oil is constituted of 51% SFA (palmitic acid), 38% MUFA, 11% PUFA [35], carotenoids, lycopene and xanthophylls [36]. Rats fed with 12% palm oil for one-year display increased total serum cholesterol levels, but lower aortic accumulation of cholesteryl esters compared to SFO, soybean and butter most likely due to the high concentration of micronutrients and MUFA in this oil [18]. Moreover, palm oil may reduce oxidative stress associated to ischemia-reperfusion injury [37]. Further studies are needed to clarify the contribution of these edible oils on human health, evaluating the role played by different fatty acids.
It is becoming evidently clear that the various dietary oils differ not only in the FA profile, but in the content of non-saponifiable species as well. Studies on olive oil have regularly been more focused on these non-saponifiable components. On the contrary, the direct role of oleic acid has been neglected. Different from other FA, oleic acid is not an essential FA, since it can be de novo synthesized by stearoyl-CoA desaturase 1 (SCD1). Exploring SCD1, the master regulator of oleic acid synthesis, may therefore offer important insights on the role of the oleic acid largely present in olive oil. In this light, in vivo and in vitro studies in which the activity of SCD1 has been shut down represent a valid opportunity to evaluate the direct contribution of oleic acid supplementation with the diet (i.e. EVOO). To date, several clinical trials are currently conducted focusing on SCD1 (Table 1) aiming to understand how nutrients may interact with the organism, regulating energy and metabolic homeostasis as well as disease progression.
Table 1. Stearoyl-CoA desaturase 1 (SCD1) clinical trials.

Trial Identifier

Trial Phase (Status)





Stearoyl-CoA Desaturase and Energy Metabolism in Humans

Behavioral: PUFA‒Cys/Met diet

Behavioral: SFA+Cys/Met diet



Fatty Acid Desaturase Gene Locus Interactions with Diet (FADSDIET2)

Dietary Supplement: LA

Dietary Supplement: ALA


Not yet recruiting

Elevated Stearoyl-CoA Desaturase-1 Expression Predicts the Disease Severity of Severe Acute Pancreatitis




Gene–Diet Interactions in Fatty Acid Desaturase 1 Gene

Dietary Supplement: Sunflower oil



Genetic Variants Modulate Association Between Dietary n-3 LCPUFAs and DHA Proportion in Breast Milk



Completed, Has Results

Fish Oil Supplementation, Nutrigenomics and Colorectal Cancer Prevention

Drug: Eicosapentanoic acid and docosahexanoic acid

Drug: Oleic Acid



Botanical Oils Study to Determine Genetic Differences in the Way Your Body Processes Fats in Edible Oils

Dietary Supplement: soybean oil and borage oil

Lipids ingested with the diet are primarily digested and absorbed in the small intestine, followed by delivery to their sites of action in the body by crossing the liver. Thus, the gastrointestinal tract and the liver are at the nexus between a vast source of nutrients and the rest of the body and are connected both anatomically and functionally. The gut-liver axis is characterized by bidirectional traffic: nutrients and factors derived from gut lumen reach the liver through the portal circulation, while bile acids are released in the small intestine from the biliary duct.
In this review, we will particularly focus on the role of the major component of olive oil—the oleic acid. We will exploit the contribution of SCD1 and its product oleic acid in health and diseases, with particular attention to the gut-liver axis. Although it might appear controversial in some cases, it is evidently clear that oleic acid plays an essential part in the development and the homeostasis of our organism, and possible disruption of its pathway may result in disease onset and progression.

2. Oleic Acid in Health and Disease

In order to characterize the role of oleic acid in health and disease, numerous studies and clinical trials have been conducted (Table 2). Several studies have highlighted the importance of MUFA in the diet, suggesting that the source and origin of MUFA is fundamental to analyse the beneficial effects of this FA [38]. In Greece, Italy and Spain, olive oil consumption constitutes approximately 60% of MUFA intake, whereas in other countries MUFAs are mainly introduced with meat products [39]. A correlation between MUFA intake and the reduction of cardiovascular heart disease risk have been described [40], whereas a subsequent meta-analysis observed no significant association [41]. These conflicting data could possibly be explained considering the different sources of MUFAs consumed by different cohorts of patients. Llorente-Cortes et al. demonstrated that a MUFA-rich diet reduced the postprandial monocytes inflammatory state linked to metabolic syndrome [42]. Indeed, MUFAs display beneficial effects on insulin sensitivity and type 2 diabetes mellitus [43]. In particular, Vessby et al. observed that the reduction of SFA and the concomitant addition of MUFA to the diet ameliorated insulin sensitivity [44]. The western diet is rich in foods with high SFA abundance such as red meat and processed foods [45]. This fat overload contributes to weight gain and the succeeding inflammation, and SFA induce insulin resistance and type 2 diabetes mellitus [46]. Palmitic acid promotes the synthesis of non-esterified fatty acids (NEFAs), ceramides and reactive oxygen species (ROS), mitochondrial dysfunction and inflammation [47][48]. SFA are able to alter the microbiota composition in the gut as well by up-regulating LPS and toll-like receptor 4 (TLR4) levels [49]. The substitution of palmitic with oleic acid in the diet is able to reverse these detrimental metabolic effects of SFA. Cell culture studies have facilitated the definition of these molecular metabolic changes. In detail, oleic acid enhances mitochondrial oxidation of SFA by increasing triacylglycerol (TAG) and by reducing diacylglycerol (DAG) and ceramide production, thus protecting the cells from inflammation [50].
Table 2. Oleic acid clinical trials.

Trial Identifier

Trial Phase (Status)





Effect of Oleic Acid on Inflammation Markers and Blood Lipid Metabolites: A Randomised, Double-Blind, Crossover Study

Novel Olein



Energy Dense Oleic Acid Formula to Geriatric Patients

Calogen®–an energy dense oleic acid-based formula



The Acute Effects of Oleic Acid Enriched diets on Lipids, Insulin Sensitivity and Serum Inflammatory Markers

Dietary Supplement: The acute effects of dietary fat on lipid profile, insulin sensitivity and inflammatory markers



Canola Oil Multi-Centre Intervention Trial II

Other: Regular Canola Oil

Other: High Oleic Canola Oil

Other: Western Type Diet–Common Dietary Oils



Canola Oil Multi-Centre Intervention Trial II

Other: Canola Oil

Other: High oleic acid canola oil

Other: Western diet oil combination



Effect of Olive Oil on Erythrocyte Membrane Fatty Acid Contents in Hemodialysis Patients

Dietary Supplement: Stir-fried olive oil group

Dietary Supplement: Natural olive oil group



Health Effects of CLA Versus Industrial Trans Fatty Acids

Procedure: Consumption of CLA enriched food



Energy Dense Formula to People Living in Old Peoples Home

Dietary Supplement: Calogen extra strawberry



Differential Metabolism of Dietary Fatty Acids

Dietary Supplement: Oleic acid (OA)

Dietary Supplement: Palmitic Acid (PA)



Fatty Acid Taste thresholds: Caproic, Lauric, Oleic, Linoleic, Linolenic

Furthermore, oleic acid displays the ability to prevent SFA-induced inflammation. In high fat diet fed mice, oleic acid administration ameliorated insulin sensitivity, reduced pro-inflammatory cytokines levels as Interleukin-1β, Interleukin-6 and Tumor Necrosis Factor-α and up-regulated the anti-inflammatory Inteleukin-10 and adiponectin levels [51]. Through this mechanism, oleic acid promotes M2 anti-inflammatory macrophages phenotype, leading to reduction of leukotriene B4 secretion and PTEN expression [52].
The peculiar beneficial role of oleic acid has been observed in several diseases including coronary heart disease, rheumatoid arthritis, and cancer. Oleic acid consumption prevents the risk of developing rheumatoid arthritis by increasing leukotriene A3 levels, a potent inhibitor of pro-inflammatory LTB4 [53]. In colorectal cancer HT-29 cells, oleic acid promotes apoptosis and cell differentiation via the downregulation of cyclooxygenase and Bcl-2 expression [54]. In breast cancer cells, oleic acid reduces the expression of the oncogene Her-2/neu and acts synergistically with anticancer drug trastuzumab [55]. Moreover, in breast tissue cells, oleic acid reduces the entering of lipid peroxidation into the phospholipid membrane of the cells [56].
Interestingly, in animal models, oleic acid is able to induce lung injury miming acute respiratory distress syndrome (ARDS). Oleic acid administration induces direct toxicity to the endothelial cells characterized by endothelial necrosis, epithelial injury and neutrophil infiltration [57][58]. Recently, it has been demonstrated that Liver X Receptor (LXR) activation protects the lungs from oleic acid-induced ARDS by decreasing the inflammatory response and by promoting antioxidant capacity [59]. On the other hand, in lung cancer, oleic acid exerts beneficial effects through promotion of apoptosis, mitosis arrest and cellular differentiation and by inhibiting angiogenesis [60]. In murine models, Piegari et al. have shown that an oleic acid-enriched diet ameliorated animal survival and lung tumour latency, confirming the oleic acid anticancer properties [61].
Finally, oleic acid displays a pivotal role in the development of the brain, the organ with the highest lipid content of the body second to white adipose tissue. In this organ, lipids are essential for the correct homeostasis and alterations in lipid metabolism are linked to neurological diseases [62]. Oleic acid is the only FA synthesized by astrocytes and it acts as a neurotrophic factor for neurons [63]. In astrocytes, albumin uptake and transcytosis via endoplasmic reticulum induces sterol regulatory element-binding protein-1 (SREBP-1) and stearoyl-CoA desaturase expression, causing oleic acid production. The synthesized oleic acid promotes axonal and dendrite growth and induces doublecortin expression, resulting in neuron migration [64][65][66]. These data confirm the pivotal role of oleic acid in astrocyte-neuron crosstalk and further studies should be performed in order to evaluate the role of oleic acid in neurodegenerative disorders. Given the crucial role of oleic acid in brain metabolism, Priore et al. treated C6 glioma cells with oleic acid and hydroxytyrosol and observed a reduction in de novo fatty acid and cholesterol synthesis, a crucial step in human glial cells malignancy [67][68].

3. SCD1: The Oleic Acid Producer

SCD is an enzyme anchored to the endoplasmic reticulum, where it catalyzes the biosynthesis of MUFA from SFA, either derived from the diet or synthesized de novo. SCD is Δ9-fatty acyl CoA desaturases that catalyzes the formation of a double bond in the cis-delta-9 position of saturated fatty acyl CoA. The preferred substrates of SCD are palmitic (C16:0) and stearic (C18:0) acids, which are converted into palmitoleic (C16:1 n-7) and oleic (C18:1 n-9) acids, respectively [69] (Figure 1). These products are the most abundant MUFA incorporated into different lipid species, including triglycerides, wax esters, cholesterol esters, and phospholipids [70]. The ratio of SFA to MUFA is important to modulate phospholipid composition, and an unbalanced ratio toward SFA production is linked to multiple pathological conditions including obesity, diabetes, cardiovascular and neurological diseases, and cancer [71]. Moreover, MUFAs serve as mediators of signal transduction and cellular differentiation [71]. Thus, the expression of SCD is highly important in both physiological and pathological conditions and SCD is consequently tightly controlled at both transcriptional and post-translational level. Numerous dietary and hormonal signals and several transcription factors such as LXR, SREBP1C, carbohydrate response element binding protein (ChREBP), peroxisome proliferator activated receptor (PPAR), and estrogen receptor (ER) are involved in SCD transcriptional control [72][73].
Figure 1. Scheme representing the biosynthesis of MUFA in animals. Stearoyl CoA Desaturase 1 (SCD1) catalyzes the rate-limiting step for the conversion of saturated fatty acid (SFA) into monounsaturated ones (MUFA). (ACC—acetyl CoA carboxylase; FASN—fatty acid synthase; ELOVL6—fatty acid elongases 6).
SCD is a highly conserved enzyme with multiple isoforms sharing similarities in protein sequences [74]. To date, two human isoforms (1 and 5) and four mouse SCD isoforms (SCD1-4) have been identified [75][76]. Despite a distinct distribution pattern, the different isoforms share the equal enzymatic function. Particularly, in both human and mice, SCD1 represents the predominant isoform and it is ubiquitously expressed among tissues, with constitutively high levels in lipogenic tissues, such as liver and white adipose tissue [74]. Contrarily, SCD5 is unique to primates and is highly expressed in brain and pancreas [76]. In adult mice, Scd2 isoform is ubiquitously expressed in most tissues except for the liver, whereas Scd3 and Scd4 expression is more restricted [77][78][79].
The existence of multiple SCD1 isoforms, sharing a high sequence homology and catalyzing the same biochemical reaction, poses difficulties in order to distinguish the role of each single isoform and its metabolic contribution. To this end, substantial insights into SCD1 functions have been gained by the use of specific mouse models, in which the expression of SCD1 is downregulated or its activity is inhibited. Several genetically engineered whole body and tissue specific SCD1 knockout models have been utilized [80] as well as Asebia mice, characterized by a whole-body deficiency of SCD1 due to a spontaneous mutation within the SCD1 gene [81]. Additionally, mice treated with antisense oligonucleotides (ASO) against SCD1—which reduces SCD1 expression in liver and adipose tissue—have been extensively employed [82]. Finally, various selective inhibitors targeting SCD1 activity have enabled the clarification of the role of this enzyme. Overall, these models demonstrate that SCD1 is a master regulator of lipid metabolism and is deeply involved in body weight regulation [83][84]. This is specifically highlighted by the resistance to diet-induced obesity and hepatic steatosis observed in SCD1 deficient mice [85]. These effects are predominantly derived from an increase in FA oxidation and thermogenesis, as well as a reduced lipid synthesis. The increased FA oxidation is mainly explained by a defect of skin permeability in SCD1KO mice which is causing heat leak and water link. The increased lipid oxidation is mediated by the induction of the AMP-activated protein kinase (AMPK) [86], resulting in phosphorylation and inactivation of ACC. The inactivation of this enzyme reduces the cellular levels of malonyl-CoA, a substrate for FA biosynthesis, which in turn suppresses FA oxidation by inhibiting the mitochondrial carnitine palmitoyltransferase 1 (CPT1) shuttle system, which controls the import and oxidation of FA in mitochondria. Malonyl-CoA reduction in SCD1KO mice relieves the inhibition of CPT1 by directing FA into mitochondria where they are subsequently oxidized. In SCD1KO mice, the up-regulation of whole-body thermogenesis in brown adipose tissue (BAT) is mediated by the activation of PGC-1α and uncoupling protein-1, which uncouples oxidative respiration from ATP synthesis, resulting in dissipation of energy as heat [87]. These modulations result in an increased rate of basal thermogenesis and, consequently, of whole-body energy expenditure.
Although many efforts have been made utilizing total body SCD1KO mice, the confirmation that these mice display altered skin permeability enhancing energy expenditure and protection from high fat diet-induced obesity [88], has led to the generation of tissue specific SCD1KO mice in order to study the contribution of this enzyme to metabolic disorders and related diseases.

4. SCD1 in the Gut-Liver Axis

The liver plays a central role as a metabolic hub, where multiple biochemical processes converge to render food nutrients available to the rest of the body. However, an unbalanced diet—rich in lipid and carbohydrates—together with a sedentary lifestyle, may severely compromise the hepatic health status. Indeed, it has been shown that a high energy intake with a concomitant low energy expenditure resulted in hepatic lipid accumulation, one of the key features of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common disease of the Western Countries, characterized by a spectrum of conditions that vary from hepatic steatosis to severe form of non-alcoholic steatohepatitis (NASH), which may eventually progress toward cirrhosis and end-stage liver diseases [89]. Despite the large amount of studies focused on the impact of hepatic metabolic alterations leading to the toxic effects of excess lipids and promotes liver diseases, it is now clear that metabolites from other organs may account for disease progression, such as adipose tissue and gut, as well. Whereas the communication between the adipose tissue and the liver has been extensively investigated, the gut-liver cross-talk exploration is just at the beginning. Not only the liver can influence the gut phenotype via bile acids or metabolites, but the gut harboring microbiota and secretory factors as well can affect the hepatic health status and promote lipid accumulation. However, accumulating data show that the total amount of lipids is not the major determinant of lipotoxicity, but that specific classes of lipids (palmitic acid, cholesterol, ceramides) promote cellular damage and disease progression [90].


  1. Vannice, G.; Rasmussen, H. Position of the academy of nutrition and dietetics: Dietary fatty acids for healthy adults. J. Acad. Nutr. Diet. 2014, 114, 136–153.
  2. Diniz, Y.S.; Cicogna, A.C.; Padovani, C.R.; Santana, L.S.; Faine, L.A.; Novelli, E.L. Diets rich in saturated and polyunsaturated fatty acids: Metabolic shifting and cardiac health. Nutrition 2004, 20, 230–234.
  3. Piomelli, D. A fatty gut feeling. Trends Endocrinol. Metab. 2013, 24, 332–341.
  4. Das, U.N. Gamma-linolenic acid, arachidonic acid, and eicosapentaenoic acid as potential anticancer drugs. Nutrition 1990, 6, 429–434.
  5. Das, U.N. A defect in the activity of Delta6 and Delta5 desaturases may be a factor in the initiation and progression of atherosclerosis. Prostaglandins Leukot. Essent. Fatty Acids 2007, 76, 251–268.
  6. Ghobadi, S.; Hassanzadeh-Rostami, Z.; Mohammadian, F.; Zare, M.; Faghih, S. Effects of Canola Oil Consumption on Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. J. Am. Coll. Nutr. 2019, 38, 185–196.
  7. Kris-Etherton, P.M.; Harris, W.S.; Appel, L.J.; Nutrition, C.; American Heart Association. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002, 106, 2747–2757.
  8. Trichopoulou, A. Mediterranean diet, traditional foods, and health: Evidence from the Greek EPIC cohort. Food Nutr. Bull. 2007, 28, 236–240.
  9. Bester, D.; Esterhuyse, A.J.; Truter, E.J.; van Rooyen, J. Cardiovascular effects of edible oils: A comparison between four popular edible oils. Nutr. Res. Rev. 2010, 23, 334–348.
  10. Owen, R.W.; Mier, W.; Giacosa, A.; Hull, W.E.; Spiegelhalder, B.; Bartsch, H. Phenolic compounds and squalene in olive oils: The concentration and antioxidant potential of total phenols, simple phenols, secoiridoids, lignansand squalene. Food Chem. Toxicol. 2000, 38, 647–659.
  11. Servili, M.; Sordini, B.; Esposto, S.; Urbani, S.; Veneziani, G.; Di Maio, I.; Selvaggini, R.; Taticchi, A. Biological Activities of Phenolic Compounds of Extra Virgin Olive Oil. Antioxidants 2013, 3, 1–23.
  12. Bermudez, B.; Lopez, S.; Ortega, A.; Varela, L.M.; Pacheco, Y.M.; Abia, R.; Muriana, F.J. Oleic acid in olive oil: From a metabolic framework toward a clinical perspective. Curr. Pharm. Des. 2011, 17, 831–843.
  13. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on the substantiation of health claims related to polyphenols in olive and protection of LDL particles from oxidative damage (ID 1333, 1638, 1639, 1696, 2865), maintenance of normal blood HDL cholesterol concentrations (ID 1639), mainte. EFSA J. 2011, 9, 2033.
  14. U.S. Food and Drug Administration. FDA Completes Review of Qualified Health Claim Petition for Oleic Acid and the Risk of Coronary Heart Disease. Available online: (accessed on 10 August 2019).
  15. Aguilera, C.M.; Mesa, M.D.; Ramirez-Tortosa, M.C.; Nestares, M.T.; Ros, E.; Gil, A. Sunflower oil does not protect against LDL oxidation as virgin olive oil does in patients with peripheral vascular disease. Clin. Nutr. 2004, 23, 673–681.
  16. Navarro, M.D.; Hortelano, P.; Periago, J.L.; Pita, M.L. Effect of dietary olive and sunflower oils on the lipid composition of the aorta and platelets and on blood eicosanoids in rats. Arterioscler. Thromb. 1992, 12, 830–835.
  17. Charnock, J.S.; Sundram, K.; Abeywardena, M.Y.; McLennan, P.L.; Tan, D.T. Dietary fats and oils in cardiac arrhythmia in rats. Am. J. Clin. Nutr. 1991, 53, 1047S–1049S.
  18. Girardet, M.; Jacotot, B.; Mendy, F.; Piganeau, P.; Beaumont, J.L. Effects of edible oils on blood and arterial lipids in rats after one year’s balanced normolipidic diet. J. Med. 1977, 8, 261–278.
  19. Lambert, E.V.; Goedecke, J.H.; Bluett, K.; Heggie, K.; Claassen, A.; Rae, D.E.; West, S.; Dugas, J.; Dugas, L.; Meltzeri, S.; et al. Conjugated linoleic acid versus high-oleic acid sunflower oil: Effects on energy metabolism, glucose tolerance, blood lipids, appetite and body composition in regularly exercising individuals. Br. J. Nutr. 2007, 97, 1001–1011.
  20. Metcalf, R.G.; James, M.J.; Gibson, R.A.; Edwards, J.R.; Stubberfield, J.; Stuklis, R.; Roberts-Thomson, K.; Young, G.D.; Cleland, L.G. Effects of fish-oil supplementation on myocardial fatty acids in humans. Am. J. Clin. Nutr. 2007, 85, 1222–1228.
  21. Mozaffarian, D.; Prineas, R.J.; Stein, P.K.; Siscovick, D.S. Dietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans. J. Am. Coll. Cardiol. 2006, 48, 478–484.
  22. Dyerberg, J.; Bang, H.O.; Stoffersen, E.; Moncada, S.; Vane, J.R. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet 1978, 2, 117–119.
  23. Investigators, G.P. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet 1999, 354, 447–455.
  24. Burr, M.L.; Fehily, A.M.; Gilbert, J.F.; Rogers, S.; Holliday, R.M.; Sweetnam, P.M.; Elwood, P.C.; Deadman, N.M. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and reinfarction trial (DART). Lancet 1989, 2, 757–761.
  25. Aung, T.; Halsey, J.; Kromhout, D.; Gerstein, H.C.; Marchioli, R.; Tavazzi, L.; Geleijnse, J.M.; Rauch, B.; Ness, A.; Galan, P.; et al. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77917 Individuals. JAMA Cardiol. 2018, 3, 225–234.
  26. Casula, M.; Soranna, D.; Catapano, A.L.; Corrao, G. Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected]. Atheroscler. Suppl. 2013, 14, 243–251.
  27. Djousse, L.; Akinkuolie, A.O.; Wu, J.H.; Ding, E.L.; Gaziano, J.M. Fish consumption, omega-3 fatty acids and risk of heart failure: A meta-analysis. Clin. Nutr. 2012, 31, 846–853.
  28. Goel, A.; Pothineni, N.V.; Singhal, M.; Paydak, H.; Saldeen, T.; Mehta, J.L. Fish, Fish Oils and Cardioprotection: Promise or Fish Tale? Int. J. Mol. Sci. 2018, 19, 3703.
  29. Kwak, S.M.; Myung, S.K.; Lee, Y.J.; Seo, H.G.; Korean Meta-analysis Study Group. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: A meta-analysis of randomized, double-blind, placebo-controlled trials. Arch. Intern. Med. 2012, 172, 686–694.
  30. Popoff, F.; Balaciano, G.; Bardach, A.; Comande, D.; Irazola, V.; Catalano, H.N.; Izcovich, A. Omega 3 fatty acid supplementation after myocardial infarction: A systematic review and meta-analysis. BMC Cardiovasc. Disord. 2019, 19, 136.
  31. Rizos, E.C.; Ntzani, E.E.; Bika, E.; Kostapanos, M.S.; Elisaf, M.S. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: A systematic review and meta-analysis. JAMA 2012, 308, 1024–1033.
  32. Siscovick, D.S.; Barringer, T.A.; Fretts, A.M.; Wu, J.H.; Lichtenstein, A.H.; Costello, R.B.; Kris-Etherton, P.M.; Jacobson, T.A.; Engler, M.B.; Alger, H.M.; et al. Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory from the American Heart Association. Circulation 2017, 135, e867–e884.
  33. Manson, J.E.; Cook, N.R.; Lee, I.M.; Christen, W.; Bassuk, S.S.; Mora, S.; Gibson, H.; Albert, C.M.; Gordon, D.; Copeland, T.; et al. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N. Engl. J. Med. 2019, 380, 23–32.
  34. Weitz, D.; Weintraub, H.; Fisher, E.; Schwartzbard, A.Z. Fish oil for the treatment of cardiovascular disease. Cardiol. Rev. 2010, 18, 258–263.
  35. Ong, A.S.; Goh, S.H. Palm oil: A healthful and cost-effective dietary component. Food Nutr. Bull. 2002, 23, 11–22.
  36. Choo, Y.M.; Ng, M.H.; Ma, A.N.; Chuah, C.H.; Hashim, M.A. Application of supercritical fluid chromatography in the quantitative analysis of minor components (carotenes, vitamin E, sterols, and squalene) from palm oil. Lipids 2005, 40, 429–432.
  37. Narang, D.; Sood, S.; Thomas, M.K.; Dinda, A.K.; Maulik, S.K. Effect of dietary palm olein oil on oxidative stress associated with ischemic-reperfusion injury in isolated rat heart. BMC Pharm. 2004, 4, 29.
  38. Schwingshackl, L.; Hoffmann, G. Monounsaturated fatty acids, olive oil and health status: A systematic review and meta-analysis of cohort studies. Lipids Health Dis. 2014, 13, 154.
  39. Linseisen, J.; Welch, A.A.; Ocke, M.; Amiano, P.; Agnoli, C.; Ferrari, P.; Sonestedt, E.; Chajes, V.; Bueno-de-Mesquita, H.B.; Kaaks, R.; et al. Dietary fat intake in the European Prospective Investigation into Cancer and Nutrition: Results from the 24-h dietary recalls. Eur. J. Clin. Nutr. 2009, 63 (Suppl. 4), S61–S80.
  40. Skeaff, C.M.; Miller, J. Dietary fat and coronary heart disease: Summary of evidence from prospective cohort and randomised controlled trials. Ann. Nutr. Metab. 2009, 55, 173–201.
  41. Chowdhury, R.; Warnakula, S.; Kunutsor, S.; Crowe, F.; Ward, H.A.; Johnson, L.; Franco, O.H.; Butterworth, A.S.; Forouhi, N.G.; Thompson, S.G.; et al. Association of dietary, circulating, and supplement fatty acids with coronary risk: A systematic review and meta-analysis. Ann. Intern. Med. 2014, 160, 398–406.
  42. Llorente-Cortes, V.; Estruch, R.; Mena, M.P.; Ros, E.; Gonzalez, M.A.; Fito, M.; Lamuela-Raventos, R.M.; Badimon, L. Effect of Mediterranean diet on the expression of pro-atherogenic genes in a population at high cardiovascular risk. Atherosclerosis 2010, 208, 442–450.
  43. Palomer, X.; Pizarro-Delgado, J.; Barroso, E.; Vazquez-Carrera, M. Palmitic and Oleic Acid: The Yin and Yang of Fatty Acids in Type 2 Diabetes Mellitus. Trends Endocrinol. Metab. 2018, 29, 178–190.
  44. Vessby, B.; Uusitupa, M.; Hermansen, K.; Riccardi, G.; Rivellese, A.A.; Tapsell, L.C.; Nalsen, C.; Berglund, L.; Louheranta, A.; Rasmussen, B.M.; et al. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. Diabetologia 2001, 44, 312–319.
  45. World Health Organization. Obesity and Overweight. Available online: (accessed on 10 August 2019).
  46. Lundman, P.; Boquist, S.; Samnegard, A.; Bennermo, M.; Held, C.; Ericsson, C.G.; Silveira, A.; Hamsten, A.; Tornvall, P. A high-fat meal is accompanied by increased plasma interleukin-6 concentrations. Nutr. Metab. Cardiovasc. Dis. 2007, 17, 195–202.
  47. Ertunc, M.E.; Hotamisligil, G.S. Lipid signaling and lipotoxicity in metaflammation: Indications for metabolic disease pathogenesis and treatment. J. Lipid Res. 2016, 57, 2099–2114.
  48. Tumova, J.; Andel, M.; Trnka, J. Excess of free fatty acids as a cause of metabolic dysfunction in skeletal muscle. Physiol. Res. 2016, 65, 193–207.
  49. Cani, P.D.; Amar, J.; Iglesias, M.A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A.M.; Fava, F.; Tuohy, K.M.; Chabo, C.; et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007, 56, 1761–1772.
  50. Peng, G.; Li, L.; Liu, Y.; Pu, J.; Zhang, S.; Yu, J.; Zhao, J.; Liu, P. Oleate blocks palmitate-induced abnormal lipid distribution, endoplasmic reticulum expansion and stress, and insulin resistance in skeletal muscle. Endocrinology 2011, 152, 2206–2218.
  51. Holland, W.L.; Miller, R.A.; Wang, Z.V.; Sun, K.; Barth, B.M.; Bui, H.H.; Davis, K.E.; Bikman, B.T.; Halberg, N.; Rutkowski, J.M.; et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat. Med. 2011, 17, 55–63.
  52. Camell, C.; Smith, C.W. Dietary oleic acid increases m2 macrophages in the mesenteric adipose tissue. PLoS ONE 2013, 8, e75147.
  53. Berbert, A.A.; Kondo, C.R.; Almendra, C.L.; Matsuo, T.; Dichi, I. Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition 2005, 21, 131–136.
  54. Llor, X.; Pons, E.; Roca, A.; Alvarez, M.; Mane, J.; Fernandez-Banares, F.; Gassull, M.A. The effects of fish oil, olive oil, oleic acid and linoleic acid on colorectal neoplastic processes. Clin. Nutr. 2003, 22, 71–79.
  55. Menendez, J.A.; Vellon, L.; Colomer, R.; Lupu, R. Oleic acid, the main monounsaturated fatty acid of olive oil, suppresses Her-2/neu (erbB-2) expression and synergistically enhances the growth inhibitory effects of trastuzumab (Herceptin) in breast cancer cells with Her-2/neu oncogene amplification. Ann. Oncol. 2005, 16, 359–371.
  56. Gill, C.I.; Boyd, A.; McDermott, E.; McCann, M.; Servili, M.; Selvaggini, R.; Taticchi, A.; Esposto, S.; Montedoro, G.; McGlynn, H.; et al. Potential anti-cancer effects of virgin olive oil phenols on colorectal carcinogenesis models in vitro. Int. J. Cancer 2005, 117, 1–7.
  57. Motohiro, A.; Furukawa, T.; Yasumoto, K.; Inokuchi, K. Mechanisms involved in acute lung edema induced in dogs by oleic acid. Eur. Surg. Res. 1986, 18, 50–57.
  58. Ware, L.B.; Matthay, M.A. The acute respiratory distress syndrome. N. Engl. J. Med. 2000, 342, 1334–1349.
  59. Zhao, Z.; Xu, D.; Li, S.; He, B.; Huang, Y.; Xu, M.; Ren, S.; Li, S.; Wang, H.; Xie, W. Activation of Liver X Receptor Attenuates Oleic Acid-Induced Acute Respiratory Distress Syndrome. Am. J. Pathol. 2016, 186, 2614–2622.
  60. Kimura, Y. Carp oil or oleic acid, but not linoleic acid or linolenic acid, inhibits tumor growth and metastasis in Lewis lung carcinoma-bearing mice. J. Nutr. 2002, 132, 2069–2075.
  61. Piegari, M.; Soria, E.A.; Eynard, A.R.; Valentich, M.A. Delay of Lung Adenocarcinoma (LAC-1) Development in Mice by Dietary Oleic Acid. Nutr. Cancer 2017, 69, 1069–1074.
  62. Romano, A.; Koczwara, J.B.; Gallelli, C.A.; Vergara, D.; Micioni Di Bonaventura, M.V.; Gaetani, S.; Giudetti, A.M. Fats for thoughts: An update on brain fatty acid metabolism. Int. J. Biochem. Cell Biol. 2017, 84, 40–45.
  63. Bento-Abreu, A.; Velasco, A.; Polo-Hernandez, E.; Perez-Reyes, P.L.; Tabernero, A.; Medina, J.M. Megalin is a receptor for albumin in astrocytes and is required for the synthesis of the neurotrophic factor oleic acid. J. Neurochem. 2008, 106, 1149–1159.
  64. Friocourt, G.; Koulakoff, A.; Chafey, P.; Boucher, D.; Fauchereau, F.; Chelly, J.; Francis, F. Doublecortin functions at the extremities of growing neuronal processes. Cereb. Cortex 2003, 13, 620–626.
  65. Miyazaki, M.; Kim, H.J.; Man, W.C.; Ntambi, J.M. Oleoyl-CoA is the major de novo product of stearoyl-CoA desaturase 1 gene isoform and substrate for the biosynthesis of the Harderian gland 1-alkyl-2,3-diacylglycerol. J. Biol. Chem. 2001, 276, 39455–39461.
  66. Tabernero, A.; Velasco, A.; Granda, B.; Lavado, E.M.; Medina, J.M. Transcytosis of albumin in astrocytes activates the sterol regulatory element-binding protein-1, which promotes the synthesis of the neurotrophic factor oleic acid. J. Biol. Chem. 2002, 277, 4240–4246.
  67. Prasanna, P.; Thibault, A.; Liu, L.; Samid, D. Lipid metabolism as a target for brain cancer therapy: Synergistic activity of lovastatin and sodium phenylacetate against human glioma cells. J. Neurochem. 1996, 66, 710–716.
  68. Priore, P.; Gnoni, A.; Natali, F.; Testini, M.; Gnoni, G.V.; Siculella, L.; Damiano, F. Oleic Acid and Hydroxytyrosol Inhibit Cholesterol and Fatty Acid Synthesis in C6 Glioma Cells. Oxid. Med. Cell. Longev. 2017, 2017, 9076052.
  69. Miyazaki, M.; Ntambi, J.M. Role of stearoyl-coenzyme A desaturase in lipid metabolism. Prostaglandins Leukot. Essent. Fatty Acids 2003, 68, 113–121.
  70. Miyazaki, M.; Kim, Y.C.; Ntambi, J.M. A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis. J. Lipid Res. 2001, 42, 1018–1024.
  71. Ntambi, J.M.; Miyazaki, M. Regulation of stearoyl-CoA desaturases and role in metabolism. Prog. Lipid Res. 2004, 43, 91–104.
  72. Flowers, M.T.; Ntambi, J.M. Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism. Curr. Opin. Lipidol. 2008, 19, 248–256.
  73. Liu, X.; Strable, M.S.; Ntambi, J.M. Stearoyl CoA desaturase 1: Role in cellular inflammation and stress. Adv. Nutr. 2011, 2, 15–22.
  74. Castro, L.F.; Wilson, J.M.; Goncalves, O.; Galante-Oliveira, S.; Rocha, E.; Cunha, I. The evolutionary history of the stearoyl-CoA desaturase gene family in vertebrates. BMC Evol. Biol. 2011, 11, 132.
  75. Nakamura, M.T.; Nara, T.Y. Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu. Rev. Nutr. 2004, 24, 345–376.
  76. Wang, J.; Yu, L.; Schmidt, R.E.; Su, C.; Huang, X.; Gould, K.; Cao, G. Characterization of HSCD5, a novel human stearoyl-CoA desaturase unique to primates. Biochem. Biophys. Res. Commun. 2005, 332, 735–742.
  77. Miyazaki, M.; Dobrzyn, A.; Elias, P.M.; Ntambi, J.M. Stearoyl-CoA desaturase-2 gene expression is required for lipid synthesis during early skin and liver development. Proc. Natl. Acad. Sci. USA 2005, 102, 12501–12506.
  78. Miyazaki, M.; Jacobson, M.J.; Man, W.C.; Cohen, P.; Asilmaz, E.; Friedman, J.M.; Ntambi, J.M. Identification and characterization of murine SCD4, a novel heart-specific stearoyl-CoA desaturase isoform regulated by leptin and dietary factors. J. Biol. Chem. 2003, 278, 33904–33911.
  79. Zheng, Y.; Prouty, S.M.; Harmon, A.; Sundberg, J.P.; Stenn, K.S.; Parimoo, S. Scd3—A novel gene of the stearoyl-CoA desaturase family with restricted expression in skin. Genomics 2001, 71, 182–191.
  80. AM, A.L.; Syed, D.N.; Ntambi, J.M. Insights into Stearoyl-CoA Desaturase-1 Regulation of Systemic Metabolism. TEM 2017, 28, 831–842.
  81. Zheng, Y.; Eilertsen, K.J.; Ge, L.; Zhang, L.; Sundberg, J.P.; Prouty, S.M.; Stenn, K.S.; Parimoo, S. Scd1 is expressed in sebaceous glands and is disrupted in the asebia mouse. Nat. Genet. 1999, 23, 268–270.
  82. Jiang, G.; Li, Z.; Liu, F.; Ellsworth, K.; Dallas-Yang, Q.; Wu, M.; Ronan, J.; Esau, C.; Murphy, C.; Szalkowski, D.; et al. Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase-1. J. Clin. Investig. 2005, 115, 1030–1038.
  83. Dobrzyn, A.; Ntambi, J.M. The role of stearoyl-CoA desaturase in the control of metabolism. Prostaglandins Leukot. Essent. Fatty Acids 2005, 73, 35–41.
  84. Dobrzyn, A.; Ntambi, J.M. The role of stearoyl-CoA desaturase in body weight regulation. Trends Cardiovasc. Med. 2004, 14, 77–81.
  85. Miyazaki, M.; Flowers, M.T.; Sampath, H.; Chu, K.; Otzelberger, C.; Liu, X.; Ntambi, J.M. Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis. Cell Metab. 2007, 6, 484–496.
  86. Dobrzyn, A.; Dobrzyn, P.; Lee, S.H.; Miyazaki, M.; Cohen, P.; Asilmaz, E.; Hardie, D.G.; Friedman, J.M.; Ntambi, J.M. Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing beta-oxidation in skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 2005, 288, E599–E607.
  87. Lee, S.H.; Dobrzyn, A.; Dobrzyn, P.; Rahman, S.M.; Miyazaki, M.; Ntambi, J.M. Lack of stearoyl-CoA desaturase 1 upregulates basal thermogenesis but causes hypothermia in a cold environment. J. Lipid Res. 2004, 45, 1674–1682.
  88. Sampath, H.; Flowers, M.T.; Liu, X.; Paton, C.M.; Sullivan, R.; Chu, K.; Zhao, M.; Ntambi, J.M. Skin-specific deletion of stearoyl-CoA desaturase-1 alters skin lipid composition and protects mice from high fat diet-induced obesity. J. Biol. Chem. 2009, 284, 19961–19973.
  89. Michelotti, G.A.; Machado, M.V.; Diehl, A.M. NAFLD, NASH and liver cancer. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 656–665.
  90. Marra, F.; Svegliati-Baroni, G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. J. Hepatol. 2018, 68, 280–295.
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