Gpat3-KO Mouse

GPAT3, glycerol-3-phosphate acyltransferase 3, is a key rate-limiting enzyme in triglyceride synthesis [2]. It is involved in lipid metabolism pathways and plays an important role in various biological processes such as adipogenesis, and is associated with multiple diseases [5,6]. Genetic models, like gene knockout mouse models, are valuable for studying its functions.

In several disease-related studies, GPAT3 has shown significant impacts. In hepatocellular carcinoma, its elevation reprograms triglyceride metabolism, contributing to sorafenib resistance, and pan-GPAT inhibitors can reverse this resistance [1]. In non-alcoholic fatty liver disease (NAFLD), GPAT3 deficiency attenuates corticosterone-caused hepatic steatosis and oxidative stress through the GSK3β/Nrf2 signals [2]. In a mouse model of severe congenital generalized lipodystrophy, GPAT3 deficiency alleviates insulin resistance and hepatic steatosis [4]. In Kupffer cells, loss of GPAT3 function reduces inflammation reaction, improves mitochondrial function, and inhibits the ERK signaling pathway [3]. In colorectal cancer, GPAT3-mediated lipid droplet accumulation confers chemoresistance and regulates the tumor microenvironment [6].

In conclusion, GPAT3 is crucial in lipid metabolism-related biological processes. Studies using gene knockout mouse models have revealed its roles in diseases like hepatocellular carcinoma, NAFLD, lipodystrophy, inflammation-related liver diseases, and colorectal cancer. Understanding GPAT3 functions provides potential therapeutic targets for these diseases.

References:

1. Zhou, Yu, Zhao, Huakan, Ren, Ran, Yu, Ying, Li, Yongsheng. 2024. GPAT3 is a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma. In Theranostics, 14, 3470-3485. doi:10.7150/thno.92646. https://pubmed.ncbi.nlm.nih.gov/38948063/

2. Fan, Guoqiang, Huang, Lingling, Wang, Mengxuan, Li, Yanfei, Yang, Xiaojing. 2024. GPAT3 deficiency attenuates corticosterone-caused hepatic steatosis and oxidative stress through GSK3β/Nrf2 signals. In Biochimica et biophysica acta. Molecular basis of disease, 1870, 167007. doi:10.1016/j.bbadis.2023.167007. https://pubmed.ncbi.nlm.nih.gov/38185063/

3. Fan, Guoqiang, Li, Yanfei, Zong, Yibo, Gao, Mingming, Yang, Xiaojing. 2023. GPAT3 regulates the synthesis of lipid intermediate LPA and exacerbates Kupffer cell inflammation mediated by the ERK signaling pathway. In Cell death & disease, 14, 208. doi:10.1038/s41419-023-05741-z. https://pubmed.ncbi.nlm.nih.gov/36964139/

4. Gao, Mingming, Liu, Lin, Wang, Xiaowei, Liu, George, Yang, Hongyuan. . GPAT3 deficiency alleviates insulin resistance and hepatic steatosis in a mouse model of severe congenital generalized lipodystrophy. In Human molecular genetics, 29, 432-443. doi:10.1093/hmg/ddz300. https://pubmed.ncbi.nlm.nih.gov/31873720/

5. Shan, Dandan, Li, Jian-liang, Wu, Leeying, Gimeno, Ruth E, Cao, Jingsong. 2010. GPAT3 and GPAT4 are regulated by insulin-stimulated phosphorylation and play distinct roles in adipogenesis. In Journal of lipid research, 51, 1971-81. doi:10.1194/jlr.M006304. https://pubmed.ncbi.nlm.nih.gov/20181984/

6. Wang, Ying, Xu, Caihua, Yang, Xianfeng, Li, Lihua, Huang, Zhaohui. 2024. Glycerol-3-phosphate acyltransferase 3-mediated lipid droplets accumulation confers chemoresistance of colorectal cancer. In MedComm, 5, e486. doi:10.1002/mco2.486. https://pubmed.ncbi.nlm.nih.gov/38344398/