
-   Fat-specific protein 27(FSP27) inhibits lipolysis by facilitating the inhibitory effect of transcription factor Egr1 on transcription of adipose triglyceride lipase (ATGL) [PMID: 24742676].
-   Peroxisomal beta-oxidation acts as a sensor for intracellular fatty acids and regulates lipolysis. Changes in ROS levels are sensed by PEX2, which modulates ATGL levels through post-translational ubiquitination [PMID: 34903883].
-   lncRNA-NEAT1 was found to modulate ATGL expression and disrupt lipolysis in hepatocellular carcinoma (HCC) cells. ATGL and its products, DAG and FFA, were shown to be responsible for NEAT1-mediated HCC cell proliferation. NEAT1 regulated ATGL expression by binding miR-124-3p. The miR-124-3p/ATGL/DAG+FFA/PPARalpha signaling seems to mediate the ATGL dependent cell growth [PMID: 29764424].

## Summary

The Pnpla2 gene, encoding adipose triglyceride lipase (ATGL), is central in the mobilization of energy stores in skeletal muscle, particularly under conditions of energy stress such as exercise, fasting, or disease [CS: 10]. In situations where the body requires additional energy, such as during prolonged physical activity or illness, ATGL's role in hydrolyzing triglycerides into free fatty acids becomes crucial [CS: 9]. These free fatty acids are then utilized by the muscle cells for energy production [CS: 9]. In diseases or toxicities affecting skeletal muscle, the dysregulation of Pnpla2 disrupts this critical energy liberation process [CS: 8]. For instance, in conditions like diabetes, where ATGL expression is downregulated in skeletal muscle, the reduced ability to mobilize fatty acids from triglycerides exacerbates the energy deficit in muscle cells, potentially leading to muscle weakness and impaired function [CS: 7].

Moreover, mutations in Pnpla2 cause Neutral Lipid Storage Disease with Myopathy (NLSDM), illustrating a direct link between gene dysfunction and skeletal muscle pathology [CS: 10]. These mutations lead to the production of a truncated ATGL protein, impairing its ability to efficiently hydrolyze triglycerides [CS: 9]. As a result, there is an accumulation of neutral lipids in muscle cells, hindering normal cellular function and contributing to muscle weakness and disease progression [CS: 9].
