Obesity
Obesity is a chronic, multifactorial disease characterized by excessive fat accumulation and disrupted metabolic homeostasis. It is a major risk factor for a wide range of conditions, including type 2 diabetes, cardiovascular disease, fatty liver disease, and certain cancers. Despite global awareness and lifestyle interventions, obesity prevalence continues to rise, emphasizing the urgent need for effective, targeted therapies.
Current pharmacological treatments for obesity are limited by modest efficacy, adverse effects, or poor long-term adherence. More importantly, most agents address weight loss without fully reversing the associated metabolic complications. A therapy that can safely modulate both body weight and systemic metabolic health remains elusive.
The Role of the Endocannabinoid System
Obesity is a chronic, multifactorial disease characterized by excessive fat accumulation and disrupted metabolic homeostasis. It is a major risk factor for a wide range of conditions, including type 2 diabetes, cardiovascular disease, fatty liver disease, and certain cancers. Despite global awareness and lifestyle interventions, obesity prevalence continues to rise, emphasizing the urgent need for effective, targeted therapies.
Our Approach
Our lab pioneered the development and preclinical validation of peripherally restricted CB1R antagonists, compounds that do not enter the brain, yet retain strong anti-obesity efficacy. These agents reduce body weight, improve glucose homeostasis and insulin sensitivity, and reverse metabolic abnormalities without the behavioral side effects seen in earlier CB1R-targeting drugs.
In addition to drug development, we are:
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Elucidating the role of peripheral CB1R signaling in energy metabolism and whole-body homeostasis
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Exploring combination therapies to enhance efficacy and durability of weight loss
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Identifying novel non-cannabinoid targets involved in energy homeostasis that could be then manipulated pharmacologically to restore body weight
Related Publications
Blockade of IL-6 Trans-signaling in the Presence of Certain Gut Microbiota Induces Mature-onset Obesity in Mice
Lanton T, Eidelshtein D, Rachmilewitz J, Abramovitch R, Pappo O, Udi S, Baraghithy S, Tam J, Perles S, Williams E, Elgavish S, Ruppo S, Benyamini H, Mor U, Elinav E, Schmidt-Arras D, Rehman A, Rosenstiel P, Giannou A, Huber S, Rose-John S, Galun E, Axelrod J.H
Blockade of IL-6 Trans-signaling in the Presence of Certain Gut Microbiota Induces Mature-onset Obesity in Mice
Lanton T, Eidelshtein D, Rachmilewitz J, Abramovitch R, Pappo O, Udi S, Baraghithy S, Tam J, Perles S, Williams E, Elgavish S, Ruppo S, Benyamini H, Mor U, Elinav E, Schmidt-Arras D, Rehman A, Rosenstiel P, Giannou A, Huber S, Rose-John S, Galun E, Axelrod J.H
Blockade of IL-6 Trans-signaling in the Presence of Certain Gut Microbiota Induces Mature-onset Obesity in Mice
Lanton T, Eidelshtein D, Rachmilewitz J, Abramovitch R, Pappo O, Udi S, Baraghithy S, Tam J, Perles S, Williams E, Elgavish S, Ruppo S, Benyamini H, Mor U, Elinav E, Schmidt-Arras D, Rehman A, Rosenstiel P, Giannou A, Huber S, Rose-John S, Galun E, Axelrod J.H
