The role and regulation of phospholipase D in metabolic disorders

Phospholipase D (PLD) is an enzyme that catalyzes the hydrolysis of phosphatidylcholine into phosphatidic acid and free choline. In mammals, PLD exists in two well-characterized isoforms, PLD1 and PLD2, and it plays pivotal roles as signaling mediators in various cellular functions, such as cell survival, differentiation, and migration. These isoforms are predominantly expressed in diverse cell types, including many immune cells, such as monocytes and macrophages, as well as non-immune cells, such as epithelial and endothelial cells. Several previous studies have revealed that the stimulation of these cells leads to an increase in PLD expression and its enzymatic products, potentially influencing the pathological responses in a wide spectrum of diseases. Metabolic diseases, exemplified by conditions, such as diabetes, obesity, hypertension, and atherosclerosis, pose significant global health challenges. Abnormal activation or dysfunction of PLD emerges as a potential contributing factor to the pathogenesis and progression of these metabolic disorders. Therefore, it is crucial to thoroughly investigate and understand the intricate relationship between PLD and metabolic diseases. In this review, we provide an in-depth overview of the functional roles and molecular mechanisms of PLD involved in metabolic diseases. By delving into the intricate interplay between PLD and metabolic disorders, this review aims to offer insights into the potential therapeutic interventions.