Glycerol-3-phosphate acyltransferase 3 (GPAT3)

Glycerol-3-phosphate acyltransferase 3 (GPAT3) is an enzyme localized in the endoplasmic reticulum that catalyzes the initial and rate-limiting step of de novo triacylglycerol (TAG) biosynthesis, converting glycerol-3-phosphate and long-chain acyl-CoA to lysophosphatidic acid (LPA)[1][3][4][5]. GPAT3 is predominantly expressed in adipose tissue and is highly upregulated during adipocyte differentiation, regulated by PPARγ and insulin signaling pathways[1][5]. The enzyme plays a crucial role in lipid storage, energy metabolism, and the regulation of adipogenesis. Loss-of-function or inhibition of GPAT3 reduces triglyceride synthesis and impairs adipocyte development, while overexpression increases TAG accumulation without significantly affecting phospholipid synthesis[1][5]. GPAT3 is emerging as a metabolic disease target, with implications in obesity, type 2 diabetes, liver steatosis, and inflammation-related disorders[1][3][4][6]. In macrophages (Kupffer cells), GPAT3 regulates inflammation via LPA-ERK signaling, linking lipid metabolism with inflammatory responses[6]. Drugs such as PPARγ agonists can upregulate GPAT3, and future GPAT3 inhibitors are being considered for treating metabolic diseases, though clinical agents are not yet available[1][4].

Other names

AGPAT91-acyl-sn-glycerol-3-phosphate O-acyltransferase 9MAG1HMFN0839UNQ2753/PRO6492GPAT-3AGPAT10LPAAT-thetaMGC11324MAG-1Acyl-CoA:glycerol-3-phosphate acyltransferase 3Lung cancer metastasis-associated protein 1lysophosphatidic acid acyltransferasetestis secretory sperm-binding protein Li 213e

Activation of PPARγ increases GPAT3 expression, enhancing triacylglycerol synthesis and adipogenesis[1][2][4] Inhibition or knockdown of GPAT3 results in reduced triglyceride biosynthesis and impaired adipocyte differentiation[5] Modulation of GPAT3 activity affects LPA levels and associated inflammatory signaling in the liver[6]