Gpat4-KO Mouse

Gpat4, glycerol-3-phosphate acyltransferase 4, is an endoplasmic reticulum membrane-anchored protein. It is crucial in glycerophospholipid biosynthesis and plays a part in lipid-related metabolic pathways. In plants, land-plant-specific GPATs, including those in the GPAT4/6/8 clade, are central to cutin and suberin monomer biosynthesis [1,3]. In mammals, it is involved in processes like adipogenesis and regulation of fatty acid metabolism [4,5]. Genetic models, such as knockout mice, have been valuable in studying its functions.

In Arabidopsis, the GPAT4/6/8 clade, along with the GPAT5/7 clade, is required for root suberization. GPAT4 has an additive effect with GPAT6 in root suberin biosynthesis and a redundant role with GPAT8 in wax production [1,3]. In mice, Gpat4 global and tissue-specific knockout models have shown that its deficiency in endocardial cells provokes ER stress response, enhances ER-mit communications, and triggers the cGAS-STING pathway, affecting heart development [2]. Gpat4-null pups had growth issues during suckling, and adult mice were protected from high-fat-diet-induced obesity. In brown adipocytes, Gpat4 limits oxidation of exogenous fatty acids [4]. Also, in 3T3-L1 adipocytes, shRNA-mediated knockdown of GPAT4 did not significantly decrease GPAT activity or inhibit lipid accumulation during adipocyte differentiation as much as GPAT3 knockdown, suggesting distinct roles for GPAT4 in adipogenesis [5]. In a high-fat-diet mouse model, hippocampal GPAT4 expression was up-regulated, and it may participate in diet-induced depression through the AMPK/CREB/BDNF pathway [6].

In conclusion, Gpat4 is essential for lipid-related biological processes in both plants and animals. In animals, studies using knockout mouse models have revealed its significance in heart development, obesity-related metabolism, adipogenesis, and the development of obesity-induced depression. These findings contribute to understanding the underlying mechanisms of related diseases and may provide potential targets for intervention.