During the last few decades, there has been an epidemic increase worldwide in the prevalence of obesity and its metabolic complications, including diabetes, changes in blood lipid profile and fatty liver disease, which, in turn, can lead to coronary disease, liver cirrhosis and even cancer. There is no currently available medication that simultaneously targets all of the metabolic consequences of obesity, justifying the search for novel approaches.

 

Endocannabinoids are lipid‐like signaling molecules present in the brain as well as peripheral tissues. They interact with the same cell surface receptors, CB1 and CB2, that can also recognize the psychoactive ingredient in marijuana, and produce similar effects, such as an increase in appetite (the ‘munchies’) and increased synthesis and decreased degradation of lipids. Using animal models of obesity we found that a novel class of chemical compounds that blocks the CB1 receptor in peripheral tissues but does not penetrate into the brain, improves all of the above deleterious consequences of obesity without causing untoward neurological side effects that would occur with similar, but brain‐penetrant compounds.

 

Yet, for a successful translation of our preclinical findings to clinical practice, a better understanding of the involvement of the peripheral endocannabinoid system in the pathogenesis of obesity and its metabolic complications is still required, and is the main focus of the work done in our lab.

 

In our laboratory, we use state-of-the-art multidisciplinary approaches combining cutting-edge experimental settings to address the molecular mechanisms potentially involved in the development of different aspects of the metabolic syndrome. The projects combine molecular biology, cell biology, biochemistry, pharmacology, nanotechnology and a wide range of approaches from the single molecule level through cell cultures to genetically engineered mouse models. These research projects also include collaborations with leading researchers and physicians from Israel and abroad, which are expected to generate novel insights into pathological metabolic homeostasis and, ultimately enhance the relevance of our basic and translational studies into effective drug therapy.

 

One of the fundamental questions in the field of CB1 receptor blockade is: Can peripheral CB1 receptors be selectively targeted for therapeutic benefit? Based on our most recent innovative work, the answer is Yes! Each research aim in our lab specifically addresses this issue, with the goal of highlighting the clinical importance of peripheral CB1 receptors in the pathogenesis of obesity and its metabolic complications.