Adipose triglyceride lipase, also known as patatin-like phospholipase domain-containing protein 2 and ATGL, is an enzyme that in humans is encoded by the PNPLA2 gene.[5][6][7] ATGL catalyses the first reaction of lipolysis,[8] where triacylglycerols are hydrolysed to diacylglycerols.[9]
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ATGL has very high substrate specificity for triacylglycerols.[10] It contains a catalytic dyad using serine-aspartic acid.[9]
ATGL catalyses the first reaction of lipolysis.[8] It hydrolysis triacylglycerols to diacylglycerols[9] by attacking the fatty acid attached to carbon-3 of glycerol.
ATGL acts as a control mechanism of lipolysis, as variations in diacylglycerol concentration impact enzymes in later stages of lipolysis.[11]
Defects in ATGL can cause problems in lipolysis, leading to neutral lipid storage disease.[12] As triacylglycerols are not hydrolysed to diacylglycerols, there is a build-up of triacylglycerol droplets in granulocytes.[12]
ATGL is regulated by insulin, and is similar to structure with adiponutrin, a protein that is regulated by nutrition. When there is a lack of insulin, there is an increased expression of the ATGL protein. Because adipose tissue triglyceride is a major form of energy storage, the study of how ATGL regulation and dysregulation can lead to potential problems will increase understanding of the pathophysiology behind metabolic disorders.[13] ATGL is also the key enzyme that would be able to maintain a balance between mobilization and lipid storage. Lipolytic breakdown performed by ATGL would impact regulatory functions including but not limited to cell death, growth, signaling, metabolism, and gene expression.[14][15]
There must be mechanisms set to maintain the balance between energy storage, and energy release; a dysregulation in the equilibrium result in metabolic disorder, a prime one being diabetes.[13] Adipose Triglyceride Lipase (ATGL) can undergo activation through two different pathways: transcriptionally and through post-translational modification. Through the transcriptional pathway, Beta-adrenergic, a receptor that can form a complex with agonist such as epinephrine, results in the signal transduction pathway activation of Adipose Triglyceride Lipase (ATGL). The alternative pathway is through a post-translational modification specifically phosphorylation of a serine 406 residue located on the enzyme by a kinase known as AMP activated protein kinase (AMPK). Both pathways facilitate the activation of the enzyme, resulting in the breakdown of triglyceride.[16]
Insulin is a hormone that regulate the enzyme ATGL, it inhibits the enzyme by favoring lipid storage over lipolysis.[13] One pathway of inhibition of ATGL when insulin is present is the activation of SIRT1, which inhibits FoxO1.[16][17] Specifically, FoxO1 is repressed from localizing in the nucleus by deacetylation in adipocytes.[16][18]
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