Research
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.
