In vitro stereoselective hydrolysis of diacylglycerols by hormone-sensitive lipase

Rodríguez, Jorge A.; Ali, Yassine Ben; Abdelkafi, Slim; Mendoza, Lilia D.; Leclaire, Julien; Fotiadu, Fréderic; Buono, Gérard; Carrière, Frédéric; Abousalham, Abdelkarim

doi:10.1016/j.bbalip.2009.09.020

Cited by 37 publications

(29 citation statements)

References 38 publications

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“…In cells and tissues stimulated by ␤-adrenergic hormones and agonists, lipolysis will continue with the hydrolysis of DAGs by HSL. HSL has been shown to hydrolyze DAGs predominantly at the sn-3 position (38). This stereoselectivity is consistent with the structural characteristics of the DAG substrate provided by ATGL.…”

Section: Discussionsupporting

confidence: 59%

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Studies on the Substrate and Stereo/Regioselectivity of Adipose Triglyceride Lipase, Hormone-sensitive Lipase, and Diacylglycerol-O-acyltransferases

Eichmann

Kumari

Haas

et al. 2012

Journal of Biological Chemistry

191

174

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Background: Adipose triglyceride lipase (ATGL) degrades triacylglycerol to diacylglycerol (DAG). The stereo/regioselectivity of ATGL is unknown. Results: ATGL specifically generates sn-1,3 and, in the presence of its co-activator CGI-58, sn-1,3 and sn-2,3 DAG. Conclusion: ATGL generates distinct DAG isoforms that cannot directly enter phospholipid synthesis or activate protein kinase C. Significance: Elucidation of the stereo/regioselectivity of ATGL is crucial to understand cellular DAG metabolism and signaling.

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Section: Discussionsupporting

confidence: 59%

“…An example of a positional unspecific lipase is bile salt-stimulated lipase, which hydrolyzes all positions of TAG, generating glycerol and FAs (37). In addition to DAGs, HSL can also catabolize TAGs in vitro and in vivo and exhibit preference for sn-1/3 ester bonds within TAG (9,38).…”

Section: Discussionmentioning

confidence: 99%

Studies on the Substrate and Stereo/Regioselectivity of Adipose Triglyceride Lipase, Hormone-sensitive Lipase, and Diacylglycerol-O-acyltransferases

Eichmann

Kumari

Haas

et al. 2012

Journal of Biological Chemistry

191

174

View full text Add to dashboard Cite

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“…The optimum temperature is dependent on other reaction parameters such as the oil/alcohol molar ratio [30,31] as was observed in this study. The high accumulation of DAG is consistent with the sn-1,3 specificity of Lipozyme® [18,43] and the synthesis of TAG [44], while the overall low MAG yield compared to DAG at all the treatment combinations for all three oils may be due to faster conversion of the more soluble MAG [21].…”

Section: Discussionsupporting

confidence: 75%

Identification and Quantitation of Reaction Intermediates and Residuals in Lipase-Catalyzed Transesterified Oils by HPLC

Aryee

Phillip

Cue

et al. 2011

Appl Biochem Biotechnol

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A high-performance liquid chromatography (HPLC) unit equipped with size exclusion column and a refractive index detector was used for simultaneous monitoring, identification, and quantitation of the reaction components from lipase-catalyzed transesterification of three oils. The procedure simultaneously separated and detected the unreacted triacylglycerols (TAG), diacyl-, and monoacyl-glycerol (DAG and MAG) co-products, residual alcohol as well as free fatty acid (FFA) based on retention times. The chromatograms showed well separated and resolved peaks. The elution of the components from the transesterification reaction in increasing order was: TAG < DAG < FFA < MAG. Generally, higher alcohol ratios decreased the conversion of TAG in all the oils studied with between 14% and 94% of TAG remaining at all the treatment combinations. Higher amount of salmon skin oil (SSO) TAG was generally converted to DAG than Rothsay composite (RC) and olive oil (OO) TAG. Relatively higher amount of OO DAG was converted to MAG than SSO and RC with only 5-14% DAG remaining in OO. RC and OO generally accumulated less MAG, and this was reflected as lower MAG levels in RC (<6%) and OO (<14%) compared with SSO (<27%). For the various treatment combinations and the three oils used in this study, the least amount of FFA was recorded in transesterified OO with a maximum of approximately 4%. This HPLC method can be used as a simple and fast technique to analyze the reaction components and products of transesterification reactions without the need for additional derivatization steps.

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“…The stereospecificity of ATGL has not been studied so far. Yet, similar to DG lipase, HSL hydrolyzes DG preferentially in sn-1(3) position generating 2-MG (6). Monoglyceride lipase (MGL) degrades sn-1(3) and 2-MG at identical specific rates (7).…”

Section: Monoacylglycerols (Mg)mentioning

confidence: 99%

Monoglyceride Lipase Deficiency in Mice Impairs Lipolysis and Attenuates Diet-induced Insulin Resistance

Taschler

Radner

Heier

et al. 2011

Journal of Biological Chemistry

235

223

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Monoglyceride lipase (MGL) influences energy metabolism by at least two mechanisms. First, it hydrolyzes monoacylglycerols (MG) into fatty acids and glycerol. These products can be used for energy production or synthetic reactions. Second, MGL degrades 2-arachidonoyl glycerol (2-AG), the most abundant endogenous ligand of cannabinoid receptors (CBR). Activation of CBR affects energy homeostasis by central orexigenic stimuli, by promoting lipid storage, and by reducing energy expenditure. To characterize the metabolic role of MGL in vivo, we generated an MGL-deficient mouse model (MGL-ko). These mice exhibit a reduction in MG hydrolase activity and a concomitant increase in MG levels in adipose tissue, brain, and liver. In adipose tissue, the lack of MGL activity is partially compensated by hormonesensitive lipase. Nonetheless, fasted MGL-ko mice exhibit reduced plasma glycerol and triacylglycerol, as well as liver triacylglycerol levels indicative for impaired lipolysis. Despite a strong elevation of 2-AG levels, MGL-ko mice exhibit normal food intake, fat mass, and energy expenditure. Yet mice lacking MGL show a pharmacological tolerance to the CBR agonist CP 55,940 suggesting that the elevated 2-AG levels are functionally antagonized by desensitization of CBR. Interestingly, however, MGL-ko mice receiving a high fat diet exhibit significantly improved glucose tolerance and insulin sensitivity in comparison with wild-type controls despite equal weight gain. In conclusion, our observations implicate that MGL deficiency impairs lipolysis and attenuates diet-induced insulin resistance. Defective degradation of 2-AG does not provoke cannabinoid-like effects on feeding behavior, lipid storage, and energy expenditure, which may be explained by desensitization of CBR. Monoacylglycerols (MG)3 are short lived intermediates of lipid catabolism derived from extracellular or intracellular sources. Pancreatic lipase and lipoprotein lipase generate MG by the hydrolysis of dietary triacylglycerols (TG) and circulating lipoproteins, respectively (1, 2). The lipolytic products, MG and free fatty acids (FFA), are subsequently taken up by cells, and MG are hydrolyzed into FFA and glycerol or re-esterified by the monoacylglycerol acyltransferase reaction (3). Within cells, MG are derived from the hydrolysis of glycerophospholipids or TG. Glycerophospholipids may be degraded by phospholipase C generating sn-1,2-diacylglycerols (DG), which are further hydrolyzed by sn-1-specific DG lipase resulting in the formation of 2-MG (4). The breakdown of TG is initiated by adipose triglyceride lipase (ATGL), and the produced DG is hydrolyzed by hormone-sensitive lipase (HSL) (5). The stereospecificity of ATGL has not been studied so far. Yet, similar to DG lipase, HSL hydrolyzes DG preferentially in sn-1(3) position generating 2-MG (6). Monoglyceride lipase (MGL) degrades sn-1(3) and 2-MG at identical specific rates (7). The enzyme is expressed in most cell types and is considered the rate-limiting enzyme in the degradation of MG (8, 9).In ad...

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In vitro stereoselective hydrolysis of diacylglycerols by hormone-sensitive lipase

Cited by 37 publications

References 38 publications

Studies on the Substrate and Stereo/Regioselectivity of Adipose Triglyceride Lipase, Hormone-sensitive Lipase, and Diacylglycerol-O-acyltransferases

Studies on the Substrate and Stereo/Regioselectivity of Adipose Triglyceride Lipase, Hormone-sensitive Lipase, and Diacylglycerol-O-acyltransferases

Identification and Quantitation of Reaction Intermediates and Residuals in Lipase-Catalyzed Transesterified Oils by HPLC

Monoglyceride Lipase Deficiency in Mice Impairs Lipolysis and Attenuates Diet-induced Insulin Resistance

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