Associations of Erythrocyte Fatty Acids in the De Novo Lipogenesis Pathway with Proxies of Liver Fat Accumulation in the EPIC-Potsdam Study

Abstract

Background: Biomarker fatty acids (FAs) reflecting de novo lipogenesis (DNL) are strongly linked to the risk of cardiometabolic diseases. Liver fat accumulation could mediate this relation. There is very limited data from human population-based studies that have examined this relation.

Objective: The aim of this study was to investigate the relation between specific FAs in the DNL pathway and liver fat accumulation in a large population-based study.

Methods: We conducted a cross-sectional analysis of a subsample (n = 1,562) of the EPIC-Potsdam study, which involves 27,548 middle-aged men and women. Baseline blood samples have been analyzed for proportions of 32 FAs in erythrocyte membranes (determined by gas chromatography) and biomarker concentrations in plasma. As indicators for DNL, the DNL-index (16:0 / 18:2n-6) and proportions of individual blood FAs in the DNL pathway were used. Plasma parameters associated with liver fat content (fetuin-A, ALT, and GGT) and the algorithm-based fatty liver index (FLI) were used to reflect liver fat accumulation.

Results: The DNL-index tended to be positively associated with the FLI and was positively associated with GGT activity in men (p for trend: 0.12 and 0.003). Proportions of 14:0 and 16:0 in erythrocytes were positively associated with fetuin-A, whereas 16:1n-7 were positively associated with the FLI and GGT activity (all p for trends in both sexes at least 0.004). Furthermore, the proportion of 16:1n-7 was positively related to fetuin-A in women and ALT activity in men (all p for trend at least 0.03). The proportion of 16:1n-9 showed positive associations with the FLI and GGT activity in men and fetuin-A in both sexes, whereas 18:1n-7 was positively associated with GGT activity in men (all p for trend at least 0.048).

Conclusion: Findings from this large epidemiological study suggest that liver fat accumulation could link erythrocyte FAs in the DNL pathway to the risk of cardiometabolic diseases.

Fig 1. Major products of the DNL pathway.

Acetyl-Coenzyme A (acetyl CoA) is polymerized to form FAs. The initial major product of DNL is palmitic acid (16:0) which can be transformed to palmitoleic acid (16:1n-7) by Δ9 desaturation catalyzed by the Stearoyl-Coenzyme A desaturase and subsequently elongated to cis-vaccenic acid (18:1n-7) or elongated to stearic acid (18:0) and subsequently desaturated to oleic acid (18:1n-9). Myristic acid (14:0) is another possible minor product of FA synthesis. Experimental studies found that 7-hexadecanoic acid (16:1n-9) could be derived from the β-oxidation of 18:1n-9 [21]. The DNL-index is the ratio of the endogenously produced palmitic acid (16:0), the main product of DNL, and the essential FA linoleic acid (18:2n-6) whose origin is from dietary lipids. The DNL-index has been proposed as a tool to assess FA synthesis in humans [19,20].