Guoqiang Fan,Lingling Huang,Mengxuan Wang,Haoran Kuang,Yanfei Li,Xiaojing Yang
The development of nonalcoholic fatty liver disease (NAFLD) may worsen due to chronic stress or prolonged use of glucocorticoids . Glycerol-3-phosphate acyltransferase 3 (GPAT3), has a function in obesity and serves as a key rate-limiting enzyme that regulates triglyceride synthesis. However, the precise impact of GPAT3 on corticosterone (CORT)-induced NAFLD and its underlying molecular mechanism remain unclear. For our in vivo experiments, we utilized male and female mice that were GPAT3 −/− and wild type (WT) and treated them with CORT for a duration of 4 weeks. In our in vitro experiments, we transfected AML12 cells with GPAT3 siRNA and subsequently treated them with CORT. Under CORT-treated conditions, the absence of GPAT3 greatly improved obesity and hepatic steatosis while enhancing the expression of genes involved in fatty acid oxidation , as evidenced by our findings. In addition, the deletion of GPAT3 significantly inhibited the production of reactive oxygen species (ROS), increased the expression of antioxidant genes, and recovered the mitochondrial membrane potential in AML12 cells treated with CORT. In terms of mechanism, the absence of GPAT3 encouraged the activation of the glycogen synthase kinase 3β (GSK3β)/nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway, which served as a defense mechanism against liver fat accumulation and oxidative stress . Furthermore, GPAT3 expression was directly controlled at the transcriptional level by the glucocorticoid receptor (GR). Collectively, our findings suggest that GPAT3 deletion significantly alleviated hepatic steatosis and oxidative stress through promoting GSK3β/Nrf2 signaling pathways .
Mengxuan Wang,Wanshan Gu,Zhengyao Sheng,Guoqiang Fan,Xiaojing Yang
As metabolic disorders associated with excessive lipid deposition in skeletal muscle rise, strategies to alleviate this accumulation have emerged as a major focus in metabolic research. Glycerol-3-phosphate acyltransferase 3 (GPAT3) is a key enzyme in triglyceride biosynthesis; however, its role in muscle lipid metabolism remains unclear. In this study, we overexpressed or knocked down GPAT3 in C2C12 myoblasts to evaluate its effects on muscle lipid metabolism and then validated the findings in GPAT3 knockout (KO) mice. GPAT3 deficiency significantly reduced lipid deposition in muscle cells. In C2C12 cells, changes in GPAT3 expression were accompanied by alterations in AMPK signaling activity. These results demonstrate that GPAT3 promotes lipid deposition in skeletal muscle. Our in vitro data reveal a correlation between GPAT3 and AMPK signaling; further in vivo validation and functional assays are required to clarify the role of AMPK in this process. This study highlights GPAT3 as a potential therapeutic target for metabolic diseases characterized by excessive intramuscular lipids.
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