GPAT3 is associated with lipid deposition and AMPK signaling in skeletal muscle.

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.