👤 Ewa Harasim-Symbor

Atrial fibrillation (AF) has become the most common arrhythmia of clinical importance. A well-established and recommended therapeutic option for AF is the balloon-based cryoablation (CBA) method. There are still no sensitive biomarkers for AF prediction and cryoablation effectiveness assessment, therefore in our prospective study, we examined the plasma content of apolipoproteins (Apo) and sphingolipids, as well as the distribution of selected sphingolipids among lipoprotein fractions. The study included 33 patients with AF on admission and 24 h after cryoablation therapy, while 20 healthy volunteers were recruited to the control group. Plasma Apo concentrations were determined using a multiplex assay kit measuring fluorescence signal, whereas the high-performance liquid chromatography (HPLC) method was applied to assess the total plasma sphingolipid levels as well as their content in isolated lipoprotein fractions. Our results showed that cryoballoon ablation in AF patients markedly reduced the level of almost all Apo compared to the individuals from the control and Pre-CBA groups (Apo-A1: -25.9% and -20.0%, Apo-A2: -19.9% and -17.3%, Apo-B: -26.8% and -14.4%, Apo-C1: -20.3% and -13.4%, Apo-D: -15.9% and -22.2%, Apo-E: -18.3% and -14.3%, and Apo-J: -36.4% and -21.5%, p < 0.05, respectively). Importantly, the area under the curve of Apo-J (AUC 0.81; 95% CI, 0.71-0.92) indicates that it might be a useful biomarker of cryotherapy success in AF patients. Moreover, we also observed a pronounced increase in sphinganine (Sa; +33.5%), sphingosine (So; +24.6%), sphinganine-1-phosphate (Sa1P; +34.3%), and sphingosine-1-phosphate (So1P; +22.3%) concentrations in the Pre-CBA group in comparison with controls. This is the first study that evaluates such a broad panel of Apo and sphingolipids in patients with AF undergoing the CBA procedure, however, to confirm whether any of these parameters could be a clinically useful biomarker for predicting AF or assessing the effectiveness of treatment, further research will be necessary due to limitations of the study. Show less

The production of the omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from alpha-linolenic acid (ALA) relies on the delta-6 desaturase (D6D) enzyme encoded by the Fads2 gene. While EPA and DHA reduce hepatic triacylglycerol (TAG) storage and regulate lipogenesis, the independent impact of ALA is less understood. To address this gap in knowledge, hepatic fatty acid metabolism was investigated in male wild-type (WT) and Fads2 knockout (KO) mice fed diets (16% kcal from fat) containing either lard (no n-3 LCPUFA), flaxseed oil (ALA-rich), or menhaden oil (EPA/DHA rich) for 21 weeks. Fat content and composition, as well as markers of lipogenesis, glyceroneogenesis, and TAG synthesis, were analyzed using histology, gas chromatography, and reverse transcription quantitative PCR (RT-qPCR). Mice fed the menhaden diet had significantly lower hepatic TAG compared to both lard- and flax-fed mice, concomitant with changes in n-3 and n-6 LCPUFA in both TAG and phospholipid (PL) fractions (all P < 0.05). Flax-fed WT mice had lower liver TAG content compared to their KO counterparts. Menhaden-fed mice had significantly lower expression of key lipogenic (Scd1, Srebp-1c, Fasn, Fads1, and Fads2), glyceroneogenic (Pck1), and TAG synthesis (Agpat3) genes compared to lard, with flax-fed mice showing some intermediate effects. Gene expression effects were independent of D6D activity, since no differences were detected between WT and KO mice fed the same diet. This study demonstrates that EPA/DHA and not ALA itself is critical for the prevention of hepatic steatosis. Show less