scholarly journals Potential of Fatty Acid Amide Hydrolase (FAAH), Monoacylglycerol Lipase (MAGL), and Diacylglycerol Lipase (DAGL) Enzymes as Targets for Obesity Treatment: A Narrative Review

2021 ◽  
Vol 14 (12) ◽  
pp. 1316
Author(s):  
Justin Matheson ◽  
Xin Ming Matthew Zhou ◽  
Zoe Bourgault ◽  
Bernard Le Foll

The endocannabinoid system (ECS) plays an integral role in maintaining metabolic homeostasis and may affect hunger, caloric intake, and nutrient absorption. Obesity has been associated with higher levels of the endogenous cannabinoid transmitters (endocannabinoids). Therefore, the ECS is an important target in obesity treatment. Modulating the enzymes that synthesize and degrade endocannabinoids, namely fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), and diacylglycerol lipase (DAGL), may be a promising strategy to treat obesity. This review aims to synthesize all studies investigating pharmacological or genetic manipulation of FAAH, MAGL, or DAGL enzymes in association with obesity-related measures. Pharmacological inhibition or genetic deletion of FAAH tended to promote an obesogenic state in animal models, though the relationships between human FAAH polymorphisms and obesity-related outcomes were heterogeneous, which could be due to FAAH having both pro-appetitive and anti-appetitive substrates. Genetic deletion of Mgll and Dagla as well as pharmacological inhibition of DAGL tended to reduce body weight and improve metabolic state in animal studies, though the effects of Mgll manipulation were tissue-dependent. Monitoring changes in body weight in ongoing clinical trials of FAAH inhibitors may clarify whether FAAH inhibition is a potential therapeutic strategy for treatment obesity. More preclinical work is needed to characterize the role of MAGL and DAGL modulation in obesity-related outcomes.

Biochemistry ◽  
2007 ◽  
Vol 46 (33) ◽  
pp. 9578-9585 ◽  
Author(s):  
Andrew Vila ◽  
Anja Rosengarth ◽  
Daniele Piomelli ◽  
Benjamin Cravatt ◽  
Lawrence J. Marnett

Platelets ◽  
2009 ◽  
Vol 20 (6) ◽  
pp. 376-385 ◽  
Author(s):  
Eleni Gkini ◽  
Dimitris Anagnostopoulos ◽  
Mary Mavri-Vavayianni ◽  
Athanasia Siafaka-Kapadai

2004 ◽  
Vol 143 (6) ◽  
pp. 774-784 ◽  
Author(s):  
Nazdar Ghafouri ◽  
Gunnar Tiger ◽  
Raj K Razdan ◽  
Anu Mahadevan ◽  
Roger G Pertwee ◽  
...  

2012 ◽  
Vol 9 (4) ◽  
pp. 801-813 ◽  
Author(s):  
Vinogran Naidoo ◽  
David A. Karanian ◽  
Subramanian K. Vadivel ◽  
Johnathan R. Locklear ◽  
JodiAnne T. Wood ◽  
...  

2021 ◽  
Author(s):  
Alex Mabou Tagne

The endocannabinoid system (ECS) modulates a variety of physiological processes, attracting considerable attention as a potential target for therapeutic intervention. This complex system is activated by the lipid-derived mediators anandamide and 2-arachidonoyl-sn-glycerol (2-AG), which mainly engage the cannabinoid receptor subtypes 1 (CB1) and 2 (CB2). The biological actions of anandamide and 2-AG are terminated by internalization and intracellular enzymatic hydrolysis catalyzed primarily by the serine hydrolases fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL), respectively. Here, we provide an overview of ECS and discuss the implications for advancing pharmacological tools that interfere with such a system as next-generation therapeutics. This review contains 4 figures, 3 tables and 41 references Keywords: Endocannabinoid; anandamide; 2-Arachidonoyl-sn-glycerol; fatty acid amide hydrolase; monoacylglycerol lipase; cannabinoid receptors; N-acylethanolamine acid amidase; Δ9-tetrahydrocannabinol.


2009 ◽  
Vol 52 (22) ◽  
pp. 7054-7068 ◽  
Author(s):  
Marion Feledziak ◽  
Catherine Michaux ◽  
Allan Urbach ◽  
Geoffray Labar ◽  
Giulio G. Muccioli ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document