European Journal of Nutrition

, Volume 58, Issue 4, pp 1561–1568 | Cite as

Dietary polyunsaturated fatty acids mediate the inverse association of stearoyl-CoA desaturase activity with the risk of fatty liver in dyslipidaemic individuals

  • Antonio J. Amor
  • Montserrat Cofán
  • Rocío Mateo-Gallego
  • Ana Cenarro
  • Fernando Civeira
  • Emilio Ortega
  • Emilio Ros
  • Aleix Sala-VilaEmail author
Original Contribution



The activity of stearoyl-CoA desaturase-1 (SCD1) is increased in non-alcoholic fatty liver disease (NAFLD). Polyunsaturated fatty acids (PUFA) inhibit SCD1, but clinical studies on whether all dietary PUFA species are equal in SCD1 inhibition are scarce. Serum phospholipids are an objective proxy of dietary intake of plant-derived PUFA (C18:2n-6, C18:3n-3) and marine-derived PUFA (C20:5n-3, C22:6n-3). In 355 participants with primary dyslipidemia, we cross-sectionally investigated whether the presumed association between surrogate markers of NAFLD and SCD1 activity is mediated by intake of PUFA, and, if it is, what PUFA species are relevant in this regard.


We determined the fatty acid profile of serum phospholipids by gas chromatography, and used the ratio C16:1n-7/C16:0 as a marker of SCD1 activity. NAFLD was diagnosed by values ≥ 60 in the fatty liver index (FLI), a surrogate recently validated against ultrasonography.


FLI ≥ 60 was detected in 37.5% (n = 133) of study participants. In a multivariate model, SCD1 activity showed an expected significant association with the risk of NAFLD, with odds ratio (OR) (95% confidence interval) of 1.44 (1.04–2.01) for each 0.01 increase. In a model further allowing the stepwise inclusion of plant-derived PUFA, marine-derived PUFA, and total PUFA (vegetable + marine), total PUFA replaced SCD1 activity as a significant (inverse) association of NAFLD, with OR 0.89 (0.81–0.99).


Total PUFA, regardless of their origin, mediates the relationship between SCD1 activity and NAFLD. This provides a new insight in the protective effects of PUFA against NAFLD, heretofore mostly focussed on PUFA species from marine origin.


Stearoyl-CoA desaturase Alpha-linolenic acid Docosahexaenoic acid Eicosapentaenoic acid Linolenic acid Non-alcoholic fatty liver disease 



Docosahexaenoic acid


Eicosapentaenoic acid


Fatty liver índex


Non-alcoholic fatty liver disease




Polyunsaturated fatty acids


Stearoyl-CoA desaturase



This work was supported by grants FIS PI06/0365 and CIBERCV from the Spanish Health Ministry and Fundació Privada Catalana de Nutrició i Lípids, Barcelona, Spain. AS-V holds a Miguel Servet fellowship from the Ministry of Economy and Competitiveness through the Instituto de Salud Carlos III, Spain (CP12/03299). Emili Corbella provided expert assistance with statistical analyses. CIBEROBN and CIBERCV are initiatives of Instituto de Salud Carlos III, Madrid, Spain.

Compliance with ethical standards

Conflict of interest

None of the authors had a personal or financial conflict of interest.


  1. 1.
    Paton CM, Ntambi JM (2009) Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab 297:E28–37. CrossRefGoogle Scholar
  2. 2.
    Cohen P, Miyazaki M, Socci ND et al (2002) Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 297:240–243CrossRefGoogle Scholar
  3. 3.
    Karpe F, Hodson L (2008) Caution on the interpretation of plasma fatty acid composition as a proxy marker for SCD1 activity: particular implications for using the 16:1/16:0 ratio in QTL studies involving hyperlipidemic patients. Arterioscler Thromb Vasc Biol 28:e152. (author reply e153) CrossRefGoogle Scholar
  4. 4.
    Attie AD, Krauss RM, Gray-Keller MP et al (2002) Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia. J Lipid Res 43:1899–1907CrossRefGoogle Scholar
  5. 5.
    Ntambi JM, Miyazaki M, Stoehr JP et al (2002) Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci USA 99:11482–11486. CrossRefGoogle Scholar
  6. 6.
    Chong MF-F, Hodson L, Bickerton AS et al (2008) Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 days of high-carbohydrate feeding. Am J Clin Nutr 87:817–823CrossRefGoogle Scholar
  7. 7.
    Puri P, Wiest MM, Cheung O et al (2009) The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology 50:1827–1838. CrossRefGoogle Scholar
  8. 8.
    Kotronen A, Seppanen-Laakso T, Westerbacka J et al (2009) Hepatic stearoyl-CoA desaturase (SCD)-1 activity and diacylglycerol but not ceramide concentrations are increased in the nonalcoholic human fatty liver. Diabetes 58:203–208. CrossRefGoogle Scholar
  9. 9.
    Erbel R, Budoff M, Subcommittee AHASC and SS et al (2012) Improvement of cardiovascular risk prediction using coronary imaging: subclinical atherosclerosis: the memory of lifetime risk factor exposure. Eur Heart J 33:1201–1213. CrossRefGoogle Scholar
  10. 10.
    Xu P, Wang H, Kayoumu A et al (2015) Diet rich in docosahexaenoic acid/eicosapentaenoic acid robustly ameliorates hepatic steatosis and insulin resistance in seipin deficient lipodystrophy mice. Nutr Metab (Lond) 12:58. CrossRefGoogle Scholar
  11. 11.
    Ntambi JM (1999) Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. J Lipid Res 40:1549–1558Google Scholar
  12. 12.
    Sekiya M, Yahagi N, Matsuzaka T et al (2003) Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 38:1529–1539. CrossRefGoogle Scholar
  13. 13.
    Warensjö E, Risérus U, Gustafsson I-B et al (2008) Effects of saturated and unsaturated fatty acids on estimated desaturase activities during a controlled dietary intervention. Nutr Metab Cardiovasc Dis 18:683–690. CrossRefGoogle Scholar
  14. 14.
    Bjermo H, Iggman D, Kullberg J et al (2012) Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr 95:1003–1012. CrossRefGoogle Scholar
  15. 15.
    Karlstrom BE, Jarvi AE, Byberg L et al (2011) Fatty fish in the diet of patients with type 2 diabetes: comparison of the metabolic effects of foods rich in n-3 and n-6 fatty acids. Am J Clin Nutr 94:26–33. CrossRefGoogle Scholar
  16. 16.
    Vessby B, Gustafsson I-B, Tengblad S, Berglund L (2013) Indices of fatty acid desaturase activity in healthy human subjects: effects of different types of dietary fat. Br J Nutr 110:871–879. CrossRefGoogle Scholar
  17. 17.
    Pérez-Heras AM, Mayneris-Perxachs J, Cofán M et al (2016) Long-chain n-3 PUFA supplied by the usual diet decrease plasma stearoyl-CoA desaturase index in non-hypertriglyceridemic older adults at high vascular risk. Clin Nutr. Google Scholar
  18. 18.
    Shapiro H, Tehilla M, Attal-Singer J et al (2011) The therapeutic potential of long-chain omega-3 fatty acids in nonalcoholic fatty liver disease. Clin Nutr 30:6–19. CrossRefGoogle Scholar
  19. 19.
    Bouzianas DG, Bouziana SD, Hatzitolios AI (2013) Potential treatment of human nonalcoholic fatty liver disease with long-chain omega-3 polyunsaturated fatty acids. Nutr Rev 71:753–771. CrossRefGoogle Scholar
  20. 20.
    Hodson L, Skeaff CM, Fielding BA (2008) Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res 47:348–380. CrossRefGoogle Scholar
  21. 21.
    Bedogni G, Bellentani S, Miglioli L et al (2006) The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 6:33. CrossRefGoogle Scholar
  22. 22.
    Pais R, Giral P, Khan J-F et al (2016) Fatty liver is an independent predictor of early carotid atherosclerosis. J Hepatol. Google Scholar
  23. 23.
    European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO) (2016) EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia 59:1121–1140. CrossRefGoogle Scholar
  24. 24.
    Sala-Vila A, Cofán M, Pérez-Heras A et al (2010) Fatty acids in serum phospholipids and carotid intima-media thickness in Spanish subjects with primary dyslipidemia. Am J Clin Nutr 92:186–193. CrossRefGoogle Scholar
  25. 25.
    Gómez-Gerique JA, Gutiérrez-Fuentes JA, Montoya MT et al (1999) Lipid profile of the Spanish population: the DRECE (diet and risk of cardiovascular disease in Spain) study. DRECE study group. Med Clin (Barc) 113:730–735Google Scholar
  26. 26.
    American Diabetes Association (2018) 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2018. Diabetes Care 41:S13–S27. CrossRefGoogle Scholar
  27. 27.
    Amor AJ, Pinyol M, Solà E et al (2017) Relationship between noninvasive scores of nonalcoholic fatty liver disease and nuclear magnetic resonance lipoprotein abnormalities: a focus on atherogenic dyslipidemia. J Clin Lipidol 11:551–561.e7. CrossRefGoogle Scholar
  28. 28.
    Burdge GC, Wright P, Jones AE, Wootton SA (2000) A method for separation of phosphatidylcholine, triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid-phase extraction. Br J Nutr 84:781–787CrossRefGoogle Scholar
  29. 29.
    Yokozawa J, Sasaki T, Ohwada K et al (2009) Down-regulation of hepatic stearoyl-CoA desaturase 1 expression by angiotensin II receptor blocker in the obese fa/fa Zucker rat: possible role in amelioration of insulin resistance and hepatic steatosis. J Gastroenterol 44:583–591. CrossRefGoogle Scholar
  30. 30.
    Sampath H, Ntambi JM (2005) Polyunsaturated fatty acid regulation of genes of lipid metabolism. Annu Rev Nutr 25:317–340. CrossRefGoogle Scholar
  31. 31.
    Hodson L, Fielding BA (2013) Stearoyl-CoA desaturase: rogue or innocent bystander? Prog Lipid Res 52:15–42. CrossRefGoogle Scholar
  32. 32.
    Li ZZ, Berk M, McIntyre TM, Feldstein AE (2009) Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem 284:5637–5644. CrossRefGoogle Scholar
  33. 33.
    Bass NM (2010) Lipidomic dissection of nonalcoholic steatohepatitis: moving beyond foie gras to fat traffic. Hepatology 51:4–7. CrossRefGoogle Scholar
  34. 34.
    Zhou YE, Egeland GM, Meltzer SJ, Kubow S (2009) The association of desaturase 9 and plasma fatty acid composition with insulin resistance-associated factors in female adolescents. Metabolism 58:158–166. CrossRefGoogle Scholar
  35. 35.
    Saadatian-Elahi M, Slimani N, Chajès V et al (2009) Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 89:331–346. CrossRefGoogle Scholar
  36. 36.
    Aranceta J, Pérez Rodrigo C, Naska A et al (2006) Nut consumption in Spain and other countries. Br J Nutr 96(Suppl 2):S3–11CrossRefGoogle Scholar
  37. 37.
    Casas-Agustench P, Salas-Huetos A, Salas-Salvadó J (2011) Mediterranean nuts: origins, ancient medicinal benefits and symbolism. Public Health Nutr 14:2296–2301. CrossRefGoogle Scholar
  38. 38.
    Machado MV, Cortez-Pinto H (2013) Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatol 58:1007–1019. CrossRefGoogle Scholar
  39. 39.
    Yang BL, Wu WC, Fang KC et al (2015) External validation of fatty liver index for identifying ultrasonographic fatty liver in a large-scale cross-sectional study in Taiwan. PLoS One 10:1–13. Google Scholar
  40. 40.
    Motamed N, Sohrabi M, Ajdarkosh H et al (2016) Fatty liver index vs waist circumference for predicting non-alcoholic fatty liver disease. World J Gastroenterol 22:3023–3030. CrossRefGoogle Scholar
  41. 41.
    Gastaldelli A, Kozakova M, Højlund K et al (2009) Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population. Hepatology 49:1537–1544. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Antonio J. Amor
    • 1
    • 2
  • Montserrat Cofán
    • 1
    • 2
  • Rocío Mateo-Gallego
    • 3
  • Ana Cenarro
    • 3
  • Fernando Civeira
    • 3
  • Emilio Ortega
    • 1
    • 2
  • Emilio Ros
    • 1
    • 2
  • Aleix Sala-Vila
    • 1
    • 2
    Email author
  1. 1.Lipid Clinic, Endocrinology and Nutrition Service, Hospital ClínicInstitut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS)BarcelonaSpain
  2. 2.Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn)Instituto de Salud Carlos III (ISCIII)MadridSpain
  3. 3.Lipid Clinic and Molecular Research Laboratory, Hospital Universitario Miguel Servet, IIS AragónUniversidad de Zaragoza, CIBERCVZaragozaSpain

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