Agpat5, also known as 1-acylglycerol-3-phosphate O-acyltransferase 5, is a lipid regulatory enzyme involved in glycerophospholipid metabolism. It converts lysophosphatidic acid to phosphatidic acid, which is crucial for lipid biosynthesis. Agpat5 functions in various biological processes, with its role being studied using genetic mouse models [2,3,4].

In genetic mouse models, Agpat5 expressed in agouti-related peptide (AgRP) neurons is essential for insulin-induced hypoglycemia sensing and glucagon secretion. Inactivation of Agpat5 in AgRP neurons leads to increased fatty acid oxidation and ATP production, disrupting hypoglycemia sensing, while suppressing Cpt1a-dependent fatty acid import into mitochondria restores it [1]. In liver-specific Agpat5-deleted mice, when consuming a chow diet combined with liquid sucrose, there is a decrease in plasma insulin levels and improvement in glucose tolerance without body weight changes, indicating a liver-specific role in hyperinsulinemia and glucose tolerance [2].

In conclusion, Agpat5 is vital for lipid biosynthesis and plays significant roles in processes like hypoglycemia sensing and glucose metabolism. The use of gene knockout mouse models has revealed its specific functions in these physiological processes, contributing to our understanding of related disease mechanisms such as hypoglycemia-induced hormonal imbalances and diet-related glucose homeostasis disorders [1,2].