Anti-CGI-58 antibody antibody detects adipose triglyceride lipase protein. CGI-58 is required for the hydrolysis of fatty acids to generate energy and prevents cardiomyocyte lipid accumulation and dysfunction. Inhibition of triglyceride lipase increases intracellular lipid accumulation, impairs mitochondrial oxidative phosphorylation, and induces hypertrophic cardiac remodeling in mice. Cardiac-specific overexpression of CGI-58 reduces lipid accumulation and alleviates pressure overload-induced heart failure (HF) in mice.

The CGI-58 gene encodes a lysophosphatidic acid acyltransferase that preferentially accepts arachidonoyl-CoA and oleoyl-CoA as acyl donors. Mutations in CGI-58 result in Dorfman-Chanarin syndrome, a neutral lipid storage disorder with apparent ichthyosis. CGI-58 has been shown to act as an ATGL activator and promote lipid hydrolysis. However, its acyltransferase activity toward other lysophospholipids has been unknown. To address this, we generated a FLAG-tagged full-length CGI-58 cDNA and expressed it in insect cells. The recombinant CGI-58 protein exhibited LPAAT activity toward phosphatidic acid (PG) and lysophosphatidylcholine (LPC), but not lipid peroxidation products or other lysophospholipids, as determined by LC-MS analysis.

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Immunoblotting and immunoelectron microscopy confirmed that CGI-58 is localized to the lamellar granules (LGs), a group of lipid transport and secretion vesicles found in keratinocytes. In addition, LG-specific deletion of CGI-58 results in reduced PG and CL content in cultured skin fibroblasts and Dorfman-Chanarin syndrome patients. The restoration of CGI-58 expression by adeno-associated virus-9-mediated gene transfer (rAAV9-CGI-58) alleviated lipid accumulation and ER stress in CGI-58f/f and CGI-58cko mice fed a normal or HFD diet. 4-PBA treatment further mitigated lipid accumulation and ER stress in both CGI-58f/f and CGI-58cko hearts.

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