Anandamide induced PPARγ transcriptional activation and 3T3-L1 preadipocyte differentiation

Bouaboula, Monsif; Hilairet, Sandrine; Marchand, Jean; Fajas, Lluís; Fur, G. Le; Casellas, Pierre

doi:10.1016/j.ejphar.2005.05.032

Cited by 271 publications

(201 citation statements)

References 41 publications

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“…Although widely accepted as an endocannabinoid, anandamide has also been found to activate TRPV1 receptors (Zygmunt et al, 1999) and PPARg (Bouaboula et al, 2005;O'Sullivan et al, 2005). By using the ligand binding and transactivation assays (Figures 1 and 2), anandamide was further identified as a weak PPARa ligand.…”

Section: Ppara Activity Of Synthetic and Endogenous Cannabinoidsmentioning

confidence: 96%

“…THC has been shown to act on PPARg and stimulate adipocyte differentiation in cultured 3T3L1 cells, in common with other PPARg ligands (Bouaboula et al, 2005;O'Sullivan et al, 2005).…”

Section: Ppara Activity Of Synthetic and Endogenous Cannabinoidsmentioning

confidence: 99%

“…On the other hand, some cannabinoids, such as THC and anandamide, were found to stimulate adipocyte differentiation through PPARg (Bouaboula et al, 2005;O'Sullivan et al, 2005). Since PPARa and PPARg play divergent roles in lipid homeostasis, agonists with dual or triple PPAR and CB receptor activities may have potential in dyslipidaemia therapy by targeting both CNS and periphery pathways.…”

Section: Implications Of Ppara As a Target For Cannabinoidsmentioning

confidence: 99%

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Cannabinoid activation of PPARα; a novel neuroprotective mechanism

Sun

Alexander

Garle

et al. 2007

British Journal of Pharmacology

205

172

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Background and purpose: Although CB 1 receptor activation evokes neuroprotection in response to cannabinoids, some cannabinoids have been reported to be peroxisome proliferator activated receptor (PPAR) ligands, offering an alternative protective mechanism. We have, therefore, investigated the ability of a range of cannabinoids to activate PPARa and for N-oleoylethanolamine (OEA), an endogenous cannabinoid-like compound (ECL), to evoke neuroprotection. Experimental approach: Assays of PPARa occupancy and gene transactivation potential were conducted in cell-free and transfected HeLa cell preparations, respectively. In vivo estimates of PPARa activation through fat mobilization and gene transcription were conducted in mice. Neuroprotection in vivo was investigated in wild-type and PPARa gene-disrupted mice. Key results: The ECLs OEA, anandamide, noladin ether and virodhamine were found to bind to the purified PPARa ligand binding domain and to increase PPARa-driven transcriptional activity. The high affinity synthetic CB 1/2 cannabinoid agonist WIN 55212-2 bound to PPARa equipotently with the PPARa agonist fenofibrate, and stimulated PPARa-mediated gene transcription. The phytocannabinoid D 9 tetrahydrocannabinol was without effect. OEA and WIN 55212-2 induced lipolysis in vivo, while OEA pre-treatment reduced infarct volume from middle cerebral artery occlusion in wild-type, but not in PPARa-null mice. OEA treatment also led to increased expression of the NFkB-inhibitory protein, IkB, in mouse cerebral cortex, while expression of the NFkB-regulated protein COX-2 was inhibited. Conclusions and implications: These data demonstrate the potential for a range of cannabinoid compounds, of diverse structures, to activate PPARa and suggest that at least some of the neuroprotective properties of these agents could be mediated by nuclear receptor activation.

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Section: Ppara Activity Of Synthetic and Endogenous Cannabinoidsmentioning

confidence: 96%

“…THC has been shown to act on PPARg and stimulate adipocyte differentiation in cultured 3T3L1 cells, in common with other PPARg ligands (Bouaboula et al, 2005;O'Sullivan et al, 2005).…”

Section: Ppara Activity Of Synthetic and Endogenous Cannabinoidsmentioning

confidence: 99%

Section: Implications Of Ppara As a Target For Cannabinoidsmentioning

confidence: 99%

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Cannabinoid activation of PPARα; a novel neuroprotective mechanism

Sun

Alexander

Garle

et al. 2007

British Journal of Pharmacology

205

172

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“…19,23,24 In particular, and possibly relevant to our present findings, AEA, but not 2-AG, was recently reported to activate mouse adipocyte PPAR-g directly and in a way independent of CB 1 receptors. 25 AEA levels peak before adipocyte maturation and PPAR-g full expression in mouse adipocytes, and decrease significantly in hypertrophic adipocytes, where, instead, 2-AG levels and CB 1 expression remain elevated, thus mimicking the situation in the epididymal fat of mice with diet-induced obesity. 19 These previous observations indicate that, particularly at the level of the white AT, 2-AG and AEA might play different functional roles, the activity and levels only of the former compound appearing to be tightly associated with those of CB 1 receptors.…”

Section: -Arachidonoylglycerol In Abdominally Obese Males M Côté Et Almentioning

confidence: 98%

Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men

Côté

Matias

Lemieux³

et al. 2007

Int J Obes

340

176

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Objective: The link between excess intra-abdominal adiposity (IAA) and metabolic complications leading to type 2 diabetes and cardiovascular disease is well recognized. Blockade of endocannabinoid action at cannabinoid CB 1 receptors was shown to reduce these complications. Here, we investigated the relationship between IAA, circulating endocannabinoid levels and markers of cardiometabolic risk in male obese subjects. Design, subjects and measurements: Fasting plasma levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), were measured by liquid chromatography-mass spectrometry in a study sample of 62 untreated asymptomatic men with body mass index (BMI) from 18.7 to 35.2 kg/m 2 . Results: Plasma 2-AG, but not AEA, levels correlated positively with BMI, waist girth, IAA measured by computed tomography, and fasting plasma triglyceride and insulin levels, and negatively with high-density lipoprotein cholesterol and adiponectin levels. Obese men with similar BMI values (X30 kg/m 2 ) but who markedly differed in their amount of IAA (o vsX130 cm 2 , n ¼ 17) exhibited higher 2-AG levels in the presence of high IAA. No difference in 2-AG concentrations was observed between obese men with low levels of IAA vs nonobese controls. Conclusions: These results provide evidence for a relationship in men between a key endocannabinoid, 2-AG, and cardiometabolic risk factors, including IAA.

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“…Furthermore, AEA has been found dose-dependently to induce transcriptional activation of peroxisome proliferator-activated receptor (PPAR) γ, but also directly to bind to PPARγ and act as an agonist (Bouaboula et al 2005). The TRPVI antagonists capsazepine and SB366791, and the enzyme inhibitors URB597 (FAAH inhibitor) and CDC (LOX inhibitor) had no effects on the AEAinduced toxicity (Fig.…”

Section: The Cb-induced Cytotoxicity Involves Cb Receptors and The Spmentioning

confidence: 99%

Effects of cannabinoids and related fatty acids upon the viability of P19 embryonal carcinoma cells

et al. 2013

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Plym Forshell, L. et al. (2013) Effects of cannabinoids and related fatty acids upon the viability of P19 embryonal carcinoma cells. Toxicology, 87(11): 1939Toxicology, 87(11): -1951 http://dx.doi.org/10.1007/s00204-013-1051-3 Archives ofAccess to the published version may require subscription. Abstract Compounds acting on the cannabinoid (CB) receptors are involved in the control of cell fate, and there is an emerging consensus that CBs have anticancer effects. However, the CB-mediated effects are contradictory since some studies suggest stimulatory effects on cancer cell proliferation, and CBs have been shown to stimulate both proliferation and differentiation of other mitotic cells such as stem and progenitor cells. In this study, the concentration-dependent effects of synthetic and endogenous CBs on the viability of mouse P19 embryonal carcinoma (EC) cells have been examined by using fluorescence assays of cell membrane integrity, cell proliferation, oxidative stress, and detection of apoptosis and necrosis. All compounds examined produced a concentrationdependent decrease in cell viability in the micromolar range, with the potent CB receptor agonist HU 210 and the enantiomer HU 211(with no CB receptor activity) being the most potent compounds examined with apparent IC 50 values of 1 µM and 0.6 µM, respectively. The endogenous CB anandamide showed similar potency and efficacy as structurally related polyunsaturated fatty acids with no reported activity at the CB receptors. The rapid (within hours) decrease in cell viability induced by the examined CBs suggests cytocidal rather than antiproliferative effects, and is dependent on the plating cell population density with the highest toxicity around 100 cells/mm 2 . The CB-induced cytotoxicity, that appears to involve CB receptors and the sphingomyelin-ceramide pathway, is a mixture of both apoptosis and necrosis that can be blocked by the antioxidants α-tocopherol and Nacetylcysteine. In conclusion, both synthetic and endogenous CBs, produce seemingly unspecific cytotoxic effects in the P19 EC cells.

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Anandamide induced PPARγ transcriptional activation and 3T3-L1 preadipocyte differentiation

Cited by 271 publications

References 41 publications

Cannabinoid activation of PPARα; a novel neuroprotective mechanism

Cannabinoid activation of PPARα; a novel neuroprotective mechanism

Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men

Effects of cannabinoids and related fatty acids upon the viability of P19 embryonal carcinoma cells

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