Targeted metabolomics profiles serum fatty acids by HFD induced non-alcoholic fatty liver in mice based on GC-MS

Nonalcoholic fatty liver (NAFLD) is associated with metabolic abnormalities and changes in lipid processing. Fatty acids (FAs) are important signaling molecules in the body and are the main raw materials for lipid synthesis. To explore the lipidomic profile of serum fatty acids in mice, we put the mice on a high-fat diet (HFD) to induce NAFLD. We applied a targeted metabolic analysis approach using gas chromatography-mass spectrometry (GC-MS) and established a method for simultaneous determination of 36 medium and long-chain fatty acids in the serum of mice. This method was validated for linearity, range, sensitivity, precision, accuracy, recovery, stability, and dilution integrity. The levels of most FA species and total FAs were increased in the HFD group (n = 9) compared with the lean group (n = 9). The principal component analysis (PCA) and the orthogonal partial least squares discriminant analysis (OPLS-DA) of all FA species were analyzed in both groups. We found that palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), and arachidonic acid (20:4) were significantly different (VIP＞1, p＜0.05 and FC＞1.5) in the two groups. We also calculated serum indices measure the activities of different enzymes involved in fatty acid metabolism. The de novo lipogenesis index, elongase index, n-6 FAs, saturated FAs, unsaturated FAs, and SCD1 index 2 were increased in the HFD group compared with the lean group while the n-3 FAs, n-3/n-6 of the index, and SCD1 index 1 were decreased in the HFD group compared with the lean group. Relationships between major FA species and biochemical indicators (LDL-C, TC, TG, ALT, and AST) were evaluated by Pearson analysis. The serum FA concentrations (C16:0, C18:0, C18:1, and C20:4) and serum indices (De novo lipogenesis index, elongase index, saturated FAs, unsaturated FAs and n-6 FAs) positively correlated with LDL-C, TC, TG, ALT, and AST. Collectively, our study provides insights into NAFLD and its effect on lipid metabolism.