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Beyond the Scale: Exploring the Endocannabinoid System's Impact on Obesity.
Curr Diab Rep
November 2024
Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, University of Chicago, 5841 S. Maryland Ave, MC1027, Chicago, IL, 60637, USA.
Article Synopsis
- The review examines how the endocannabinoid system (ECS) affects energy balance and metabolism, highlighting its role in obesity and related disorders.
- Recent studies reveal the ECS's influence on food intake, fat storage, and insulin sensitivity, while also exploring its interactions with gut microbiota and genetic factors.
- Although past ECS-targeting treatments faced challenges, new peripherally restricted CB1 antagonists may offer safer options for managing obesity, paving the way for future research and therapeutic strategies.*
New peripherally-restricted CB1 receptor antagonists, PMG-505-010 and -013 ameliorate obesity-associated NAFLD and fibrosis.
Biomed Pharmacother
November 2024
Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea. Electronic address:
Article Synopsis
- The study investigates the potential of new compounds PMG-505-010 and PMG-505-013 as peripheral CB1 receptor antagonists aimed at treating obesity and its related complications, specifically non-alcoholic fatty liver disease (NAFLD).
- These compounds were designed to limit brain exposure by modifying rimonabant, confirmed through physicochemical analysis showing reduced lipophilicity and increased polarity.
- In experiments, the new antagonists improved metabolic health in obese mice, reversing liver injury and fibrosis while avoiding CNS side effects associated with traditional CB1R antagonists.
Charting New Territories in Obesity Management- Traditional Techniques to Tirzepatide.
Endocr Pract
January 2025
Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan.
Background: Obesity, a pervasive global health challenge affecting more than 2 billion people, requires comprehensive interventions. Traditional approaches, including lifestyle modification, and diverse drugs targeting a gastrointestinal hormone, including glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (Liraglutide, Semaglutide, Exenatide, Albiglutide, Dulaglutide, Lixisenatide, Orlistat, Phentermine/Topiramate, Lorcaserin, Sibutramine, and Rimonabant) offer tailored strategies; yet their effectiveness is limited and some drugs were taken off the market. Moreover, various surgical modalities, such as Roux-en-Y Bypass surgery, sleeve gastrectomy, intragastric balloons, biliopancreatic diversion with duodenal switch, laparoscopic adjustable gastric band, and vagal nerve blockade can be considered but are associated with numerous side effects and require careful monitoring.
View Article and Find Full Text PDFEfficacy in diet-induced obese mice of the hepatotropic, peripheral cannabinoid 1 receptor inverse agonist TM38837.
Br J Pharmacol
October 2024
7TM Pharma A/S, Hørsholm, Denmark.
Background And Purpose: The cannabinoid CB receptor has a well-established role in appetite regulation. Drugs antagonizing central CB receptors, most notably rimonabant, induced weight loss and improved the metabolic profile in obese individuals but were discontinued due to psychiatric side effects. However, metabolic benefits were only partially attributable to weight loss, implying a role for peripheral receptors, and peripherally restricted CB receptor antagonists have since been of interest.
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