Several GWAS studies have found an association between variants close to the lysophospholipase-like 1 (Lyplal1) locus and metabolic traits, including central obesity, fatty liver and waist-hip ratio (where the effect is more significant in females than males). LYPLAL1 is also upregulated in the adipose tissue of obese patients, and a mutation has been identified in a lipodystrophic patient with no other known mutation. However, the physiological role of LYPLAL1 is not fully understood. We investigated the role of LYPLAL1 using a knockout mouse model.
Lyplal1 knockout mice (C57BL/6N-Liplal1tm1b(KOMP)Wtsi, from the KOMP repository) were initially characterised on a normal chow diet by the Sanger Mouse Pipeline, with no phenotype observed. The mice were then challenged by being placed on a high fat diet (HFD) at 6 weeks of age. The phenotype of these mice was investigated up until 28 weeks of age using various tests, including DEXA body composition analysis, glucose and insulin tolerance tests and indirect calorimetry. Lyplal1-/- mice were indistinguishable from wild type mice in all in vivo tests performed. Several tissues were collected for further ex vivo analysis. Lyplal1 knockout was confirmed by Western blot. However, no effect of Lyplal1 knockout was observed on organ weight or on the expression of a range of metabolic genes. Further investigations including tissue morphology analysis and RNAseq are ongoing, to gain a better understanding of the biological role of LYPLAL1.