Dietary polyunsaturated fatty acids mediate the inverse association of stearoyl-CoA desaturase activity with the risk of fatty liver in dyslipidaemic individuals
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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.
KeywordsStearoyl-CoA desaturase Alpha-linolenic acid Docosahexaenoic acid Eicosapentaenoic acid Linolenic acid Non-alcoholic fatty liver disease
Fatty liver índex
Non-alcoholic fatty liver disease
Polyunsaturated fatty acids
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.
- 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. https://doi.org/10.1161/ATVBAHA.108.167718 (author reply e153) CrossRefGoogle Scholar
- 11.Ntambi JM (1999) Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. J Lipid Res 40:1549–1558Google Scholar
- 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. https://doi.org/10.1007/s00125-016-3902-y CrossRefGoogle Scholar
- 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
- 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. https://doi.org/10.1016/j.jacl.2017.02.001 CrossRefGoogle Scholar
- 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 84:781–787Google Scholar
- 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. https://doi.org/10.1007/s00535-009-0042-x CrossRefGoogle Scholar
- 30.Sampath H, Ntambi JM (2005) Polyunsaturated fatty acid regulation of genes of lipid metabolism. Annu Rev Nutr 25:317–340. https://doi.org/10.1146/annurev.nutr.25.051804.101917 CrossRefGoogle Scholar
- 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. https://doi.org/10.3945/ajcn.2008.26834 CrossRefGoogle Scholar