Lyplal1, or Lysophospholipase-like protein 1, is an enzyme with emerging roles in hepatic metabolism and is associated with metabolic conditions such as obesity and insulin resistance [1,2,3]. It may be involved in regulating glucose metabolism, potentially negatively regulating gluconeogenesis and upregulating glycolysis [3]. Mouse models have been crucial in studying its function.

In a mouse knockout (KO) study, Lyplal1 KO mice fed a high-fat, high-sucrose (HFHS) diet showed sex-specific differences in weight gain and fat accumulation. Female KO mice had reduced body fat percentage, while both sexes had reduced liver triglycerides and steatosis, suggesting an evolutionary conserved sex-specific effect on adiposity [1]. Another KO study indicated that Lyplal1 is dispensable for normal mouse metabolic physiology as body composition, adipose tissue distribution, and glucose response were normal in KO mice on normal chow or high-fat diet [2].

In conclusion, Lyplal1 seems to play a role in metabolic processes, especially those related to fat metabolism and glucose regulation. The gene knockout mouse models have provided insights into its sex-specific effects on adiposity and its dispensability for normal metabolic physiology, contributing to understanding its role in human obesity-related metabolic diseases.

References:

1. Vohnoutka, Rishel B, Kuppa, Annapurna, Hegde, Yash, Halligan, Brian D, Speliotes, Elizabeth K. 2023. Knockout of murine Lyplal1 confers sex-specific protection against diet-induced obesity. In Journal of molecular endocrinology, 70, . doi:10.1530/JME-22-0131. https://pubmed.ncbi.nlm.nih.gov/36748836/

2. Watson, Rachel A, Gates, Amy S, Wynn, Elizabeth H, Lelliott, Christopher J, Barroso, Inês. 2017. Lyplal1 is dispensable for normal fat deposition in mice. In Disease models & mechanisms, 10, 1481-1488. doi:10.1242/dmm.031864. https://pubmed.ncbi.nlm.nih.gov/29084768/

3. Filip, Roxana, Bélanger, Étienne, Chen, Xinhzu, Uguccioni, Spencer M, Pezacki, John Paul. 2025. LYPLAL1 enzyme activity is linked to hepatic glucose metabolism. In Biochemical and biophysical research communications, 759, 151656. doi:10.1016/j.bbrc.2025.151656. https://pubmed.ncbi.nlm.nih.gov/40147354/