Associations Between Fatty Acid Composition in Serum Cholesteryl Esters and Liver Fat, Basal Fat Oxidation, and Resting Energy Expenditure: a Population-based Study

Background: We have repeatedly shown in short-term feeding trials that a high intake of dietary n-6 PUFAs, i.e. linoleic acid, prevents liver fat accumulation compared with saturated fat. However, population-based data is lacking and the mechanisms behind such effects are unclear.

Objective: To investigate associations between serum cholesteryl ester (CE) fatty acids and liver fat, basal fat oxidation [respiratory quotient (RQ)], and resting energy expenditure (REE). We hypothesized that PUFA in particular is inversely associated with liver fat and that such a relation is partly explained by a PUFA-induced increase in basal fat oxidation or REE.

Methods: Cross-sectional analyses using linear regression models in a population-based cohort with data on serum CE fatty acid composition and liver fat (n = 308).

Results: Linoleic acid (18:2n-6) (β = -0.03, 95% CI: -0.06, -0.001) and Δ5 desaturase index were inversely associated, whereas, γ-linolenic acid (18:3n-6) (β = 0.59, 95% CI: 0.28, 0.90), dihomo-γ-linolenic acid (20:3n-6) (β = 1.20, 95% CI: 0.65, 1.75), arachidonic acid (20:4n-6) (β = 0.08, 95% CI: 0.002, 0.16), palmitoleic acid (16:1n-7) (β = 0.37, 95% CI: 0.04, 0.70), Δ6 desaturase, and stearoyl CoA desaturase-1 (SCD-1) index were directly associated with liver fat after adjustment for confounders. Several serum CE fatty acids were correlated with both liver fat and REE, but only the association between DHA (22:6n-3) and liver fat was clearly attenuated after adjustment for REE (from β = -0.63 95% CI: -1.24, -0.02 to β = -0.34, 95% CI: -0.95, 0.27). Palmitoleic acid and SCD-1 were weakly inversely correlated with RQ but could not explain a lower liver fat content.

Conclusions: Several serum CE fatty acids are associated with liver fat, among them linoleic acid. Although we identified novel associations between individual fatty acids and RQ and REE, our findings imply that PUFAs might prevent liver fat accumulation through mechanisms other than enhanced whole-body energy metabolism.