We’ve only recently discovered that body fat is not just a lump of tissue. It interacts with other systems in the body and may be regulated through cannabis.
Obesity is multifactorial, complex and chronic disease of epidemic proportions characterized by the pathological expansion of body fat. The mass increase happens for two reasons: there is a size increase of the pre-existing fat cells and then new fat cells are added. The result is endocrine and metabolic dysfunction at the level of both adipose organ and for the organism as a whole.
The endocannabinoid system (ECS) plays a key role in body fat accumulation in humans through various processes, ranging from the direct action on the fat cell to the stimulation of energy intake and the damping down of energy spending via central and peripheral mechanisms.
The lipid signaling system is made up of the following: two G-protein coupled receptors (CB1 and CB2), their endogenous polyunsaturated fatty acid ligands, endocannabinoids (ECs), and enzymes involved in their biosynthesis and degradation. This system is very well preserved throughout evolutionary time. This is suggests that the ECS plays a very big role in the biological processes responsible for energy preservation. Consequently, the ECS is critically involved in the development of obesity. It is a state where the ECS is over-activated and this represents a promising area of research for treating obesity.
Science Learns Body Fat Is Communicating With Endocrine System
For many years, adipose tissue was considered a static organ, primitive depot of fat designed to store energy and thermally isolate the organism. A Ground-breaking discovery in 1994 changed this view with the identification of a cytokine called ‘leptin.’ This is an appetite-suppressing hormone secreted by fat tissue which let us know that it is active and participating in the endocrine system. Since then, many fat-produced molecules have been identified, called adipokines, performing a crucial role in the regulation of energy balance and metabolism.
Body Fat Has Components of the Endocannabinoid System
The presence of the CB1 receptor in the adipocytes and the direct involvement of the ECS in adipocyte physiology was pinpointed by the two separate research groups in the 2003. Since the initial findings, numerous studies have explored the existence of the functional ECS in the adipocyte cells. Specifically, a few studies carried out in cultured rodent fat cells confirmed not only the presence of the CB1 , but also the whole biochemical pathway for the EC synthesis and degradation.
Fat cells produce measurable levels of the two main endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) as well as other EC-related compounds. Several studies further explored changes in the expression of ECS constituents during adipocyte differentiation. There was consistent evidence of a higher concentration of CB1 receptors as well as more of the enzymes that degrade AEA, in fat tissue. CB2 is also present in human fat cells.
Endocannabinoids and Cannabis Fight Insulin Resistance
ECS is also affects the synthesis and release of several adipokines, produced by white fat cells and these are known to impact energy balance and metabolism. Similar to leptin, insulin decreases EC levels, in this case by stimulating FAAH expression (fatty acid amide hydrolase, the enzyme degrading AEA). This negative feedback mechanism, acting on the ECS in the adipocyte are lost in obesity, which is characterized by insulin (and leptin) resistance.
Can Cannabis Target Obesity?
It is reasonable to propose that targeting adipocyte CB1 receptors in obese patients might beneficially effect lipid fluxes and the production of adipokines (leptin, adiponectin). The effect would be body weight loss (i.e. decrease food intake) and an improvement in lipid and glucose metabolism.
In addition, adipocyte CB1 receptors might be an interesting target for fat browning therapy, suggested by both in vitro and ex vivo data. The study of the browning process of the adipose tissue has attracted a lot of attention in recent years and represents a promising target for the developing a therapy target for the new anti-obesity drugs. The reasoning is that white fat contributes to the metabolic disturbances and diseases, and it is located around the abdominal area, whereas the brown fat , located on hips and thighs generates heat by burning calories, and is not considered harmful. However, whether this involvement may be relevant in vivo remains unexplored.
Further investigation of these roles might result in the discovery of novel ECS mechanisms of action, which could lead to the identification of novel drug targets for obesity and metabolic disease.
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