Exon–intron organization and chromosomal localization of the mouse monoglyceride lipase gene

Karlsson, Marie; Reue, Karen; Xia, Yu‐Rong; Lusis, Aldons J.; Langin, Dominique; Törnqvist, Hans; Holm, Cecilia

doi:10.1016/s0378-1119(01)00559-5

Cited by 80 publications

(78 citation statements)

References 14 publications

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“…Both bands disappeared after adsorption with immunizing peptide (data not shown), indicating that they represented closely related MGL isoforms. These isoforms may arise from alternative splicing (30) or from as-yet-unidentified posttranslational modification(s).…”

Section: Resultsmentioning

confidence: 99%

Brain monoglyceride lipase participating in endocannabinoid inactivation

Dinh

Carpenter

Leslie

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

1,226

972

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The endogenous cannabinoids (endocannabinoids) are lipid molecules that may mediate retrograde signaling at central synapses and other forms of short-range neuronal communication. The monoglyceride 2-arachidonoylglycerol (2-AG) meets several criteria of an endocannabinoid substance: (i) it activates cannabinoid receptors; (ii) it is produced by neurons in an activity-dependent manner; and (iii) it is rapidly eliminated. 2-AG inactivation is only partially understood, but it may occur by transport into cells and enzymatic hydrolysis. Here we tested the hypothesis that monoglyceride lipase (MGL), a serine hydrolase that converts monoglycerides to fatty acid and glycerol, participates in 2-AG inactivation. We cloned MGL by homology from a rat brain cDNA library. Its cDNA sequence encoded for a 303-aa protein with a calculated molecular weight of 33,367 daltons. Northern blot and in situ hybridization analyses revealed that MGL mRNA is heterogeneously expressed in the rat brain, with highest levels in regions where CB1 cannabinoid receptors are also present (hippocampus, cortex, anterior thalamus, and cerebellum). Immunohistochemical studies in the hippocampus showed that MGL distribution has striking laminar specificity, suggesting a presynaptic localization of the enzyme. Adenovirus-mediated transfer of MGL cDNA into rat cortical neurons increased MGL expression and attenuated N-methyl-D-aspartate/carbachol-induced 2-AG accumulation in these cells. No such effect was observed on the accumulation of anandamide, another endocannabinoid lipid. The results suggest that hydrolysis by means of MGL is a primary mechanism for 2-AG inactivation in intact neurons

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Section: Resultsmentioning

confidence: 99%

Brain monoglyceride lipase participating in endocannabinoid inactivation

Dinh

Carpenter

Leslie

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

1,226

972

View full text Add to dashboard Cite

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“…Because the MGL gene contains seven exons that can be alternatively spliced and have different 5Ј leader sequences (Karlsson et al, 2001), we designed two sets of primers to unequivocally assess for the presence of MGL mRNA in these cells and rule out any alternative splicing. One set of primers was designed to amplify the full-length MGL mRNA (i.e., 870 bp), and the second set of primers was designed to amplify a stretch of 168 bp that encode a crucial amino acid in the catalytic site of MGL (Karlsson et al, 1997) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification of a Novel Endocannabinoid-Hydrolyzing Enzyme Expressed by Microglial Cells

Muccioli¹,

Xu²,

Odah³

et al. 2007

J. Neurosci.

162

159

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The endocannabinoids (eCBs) anandamide and 2-arachidonoyl glycerol (2-AG) are inactivated by a two-step mechanism. First, they are carried into cells, and then anandamide is hydrolyzed by fatty acid amide hydrolase (FAAH) and 2-AG by monoacylglycerol lipase (MGL). Here we provide evidence for a previously undescribed MGL activity expressed by microglial cells. We found that the mouse microglial cell line BV-2 does not express MGL mRNA and yet efficiently hydrolyzes 2-AG. URB597 (3Ј-carbamoyl-biphenyl-3-ylcyclohexylcarbamate) reduces this hydrolysis by 50%, suggesting the involvement of FAAH. The remaining activity is blocked by classic MGL inhibitors [[1,1-biphenyl]-3-yl-carbamic acid, cyclohexyl ester (URB602) and MAFP (methylarachidonyl fluorophosphate)] and is unaffected by inhibitors of COXs (cyclooxygenases), LOXs (lipooxygenases), and DGLs (diacylglycerol lipases), indicating the involvement of a novel MGL activity. Accordingly, URB602 leads to selective accumulation of 2-AG in intact BV-2 cells. Although MGL expressed in neurons is equally distributed between the cytosolic, mitochondrial, and nuclear fractions, the novel MGL activity expressed by BV-2 cells is enriched in mitochondrial and nuclear fractions. A screen for novel inhibitors of eCB hydrolysis identified several compounds that differentially block MGL, FAAH, and the novel MGL activity. Finally, we provide evidence for expression of the novel MGL by mouse primary microglia in culture. Our results suggest the presence of a novel, pharmacologically distinct, MGL activity that controls 2-AG levels in microglia.

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“…MGll functions together with hormone-sensitive lipase (HSl) to hydrolyze intracellular triglyceride stores in adipocytes and other cells to fatty acids and glycerol. MGll may also complement lipoprotein lipase in completing hydrolysis of monoglycerides resulting from the degradation of lipoprotein triglycerides (16). despite this, the obesity-prone mice showed a significant increase in visceral adipose tissues.…”

Section: Discussionmentioning

confidence: 99%

Proteomic profile of visceral adipose tissues between low-fat diet-fed obesity-resistant and obesity-prone C57BL/6 mice

et al. 2010

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Abstract. certain individuals ingesting a low-fat diet are still prone to visceral obesity, and the reasons remain undetermined. This study aimed to investigate differentially expressed proteins of visceral adipose tissues between low-fat diet-fed obesity-resistant and obesity-prone c57Bl/6 mice through a proteomics approach and to ascertain potential mechanisms associated with these obesity-prone animals. First, animals were fed low-fat or normal-chow diets for 6 weeks. dietary intake and body weight were monitored during this period. after 6 weeks of the low-fat diet, obesityprone and obesity-resistant mice (noP and nor groups) were defined as those within the upper and lower quarters for weight gain, respectively. Proteomic analysis showed that ubiquinol-cytochrome c reductase core protein 1 (Uqcrc1) and enolase 3, β muscle were decreased by 8.1-and 8.8-fold in the visceral adipose tissues of the noP mice compared to the nor controls, respectively, while monoglyceride lipase (MGll) and glucose-6-phosphate dehydrogenase (G6PdH) X-linked were increased by 5.3-and 4.7-fold, respectively. These results indicate that obesity-prone animals fed low-fat diets exhibited differentially expressed proteins, e.g., Uqcrc1, enolase 3, MGll and G6PdH involved in energy metabolism, glycolysis and fat synthesis in visceral adipose tissues, which are useful for defining molecular markers and understanding the mechanisms of the development of obesity.

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Exon–intron organization and chromosomal localization of the mouse monoglyceride lipase gene

Cited by 80 publications

References 14 publications

Brain monoglyceride lipase participating in endocannabinoid inactivation

Brain monoglyceride lipase participating in endocannabinoid inactivation

Identification of a Novel Endocannabinoid-Hydrolyzing Enzyme Expressed by Microglial Cells

Proteomic profile of visceral adipose tissues between low-fat diet-fed obesity-resistant and obesity-prone C57BL/6 mice

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