Apolipoprotein B48 Knockout Ameliorates High-Fat-Diet-Induced Metabolic Impairment in Mice

This study aimed to investigate whether knockout of the <i>ApoB48</i> gene improves lipid metabolism disorders induced by a high-fat diet (HFD) in mice. Clustered regularly interspaced short palindromic repeats-Cas9 gene editing technology was used to knock out the <i>ApoB48</i> gene in C57BL/6J mice, and genotype identification showed heterozygosity (HE, <i>ApoB48</i> +/-). Subsequently, eight HE and eight wild-type (WT) mice were fed a HFD for 12 weeks. Fasting blood glucose, and insulin levels were decreased in <i>ApoB48</i> +/- mice. The intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test showed mild insulin resistance. Moreover, it delayed the development of atherosclerosis and intestinal tissue damage. Differential metabolites such as ceramide, sphingosine, and sphingosine-1-phosphate were identified using liquid chromatography-mass spectrometry, and differentially expressed proteins, including ceramide synthase 6 (CerS6), protein phosphatase 2A (PP2A), and protein kinase B (AKT), were indicated by the Kyoto Encyclopaedia of Genes and Genomes. Therefore, decreased expression of ApoB48 can ameliorate lipid metabolism disorders induced by an HFD, which may be related to the CerS6/PP2A/AKT pathway. This might represent a new approach for exploring methods to treat hyperlipidaemia.