Disease relevance of Ces3

• Microsomal triacylglycerol hydrolase (TGH) hydrolyzes stored triacylglycerol in cultured hepatoma cells (Lehner, R., and Vance, D. E. (1999) Biochem. J. 343, 1-10) [1].

High impact information on Ces3

• Carboxylesterase 3 (EC 3.1.1.1) is a major adipocyte lipase [2].
• Western blotting of subcellular fractions of WAT and confocal microscopy of fibroblasts following in vitro adipocytic differentiation are consistent with a distribution of TGH to endoplasmic reticulum, cytosol, and the lipid droplet [2].
• In the corresponding fractions, gel permeation chromatography and SDS-PAGE, followed by tandem mass spectrometric analysis of excised Coomassie Blue-stained peptides, revealed carboxylesterase 3 (triacylglycerol hydrolase (TGH); EC 3.1.1.1) [2].
• A role for Sp1 in the transcriptional regulation of hepatic triacylglycerol hydrolase in the mouse [1].
• Transcriptional activation assays in Schneider SL-2 insect cells demonstrated that Sp1 is a potent activator of the TGH promoter [1].

Biological context of Ces3

• TGH is responsible for a major part of non-HSL lipase activity in WAT in vitro and may mediate some or all HSL-independent lipolysis in adipocytes [2].
• Transient transfections of different mutant TGH promoter-luciferase constructs into 3T3-L1 adipocytes and competitive electromobility shift assays showed that the C/EBP-binding elements at positions -470/-459 bp and -404/-390 bp are important for transcriptional activation [3].
• Electrophoretic mobility shift assays demonstrated enhanced binding of nuclear proteins of adipocytes to the distal murine TGH promoter region (-542/-371 bp), yielding one adipocyte-specific migrating complex [3].
• We cloned 542 base pairs upstream of the transcriptional start site of the murine TGH gene [1].
• Dexamethasone treatment resulted in decreased TGH expression, primarily due to a dexamethasone-induced decrease in TGH mRNA stability [4].

Anatomical context of Ces3

• To explore the mechanisms that regulate TGH expression in adipose tissue, we studied the expression of TGH during the differentiation of 3T3-L1 adipocytes [3].
• A novel murine cDNA for triacylglycerol hydrolase (TGH), an enzyme that is involved in mobilization of triacylglycerol from storage pools in hepatocytes, has been cloned and expressed [5].
• Ectopic expression of C/EBPalpha in NIH 3T3 cells activated TGH mRNA expression without causing differentiation into adipocytes [3].
• The highest expression of TGH was observed in the livers of mice, with lower expression in kidney, heart, adipose and intestinal (duodenum/jejunum) tissues [5].
• Secretion of the lysosomal acid triacylglycerol hydrolase precursor by J774 macrophages [6].

Associations of Ces3 with chemical compounds

• Feeding mice diets enriched in fatty acids for 3 weeks did not affect hepatic TGH expression, though a 3-week diet enriched in fatty acids and cholesterol increased hepatic TGH expression 2-fold [7].
• To determine whether this effect correlates with inhibition of TGH activity, we investigated the ability of URB597 to inhibit triolein hydrolysis in rat liver and heart tissues, which are rich in TGH, as well as white adipose tissue (WAT), which is rich in adipose triacylglycerol lipase (TGL) and hormone-sensitive lipase [8].

Other interactions of Ces3

• J774, thioglycollate-elicited mouse peritoneal and BCG-induced rabbit alveolar macrophages all contain high levels of a triacylglycerol hydrolase (EC 3.1.1.3) (TGase) with optimal activity at pH 6 [6].

Analytical, diagnostic and therapeutic context of Ces3

• The results will permit future studies on the function of this gene via gene-targeting experiments and analysis of transcriptional regulation of the TGH gene [5].

References