Endocannabinoid system and its implications for obesity and cardiometabolic risk
1 Department of Cardiovascular Medicine, Lahey Clinic Medical Center, 41 Mall Road, Burlington, MA 01805, USA
2 Department of Anesthesiology, University of Washington School of Medicine, Box 356540, HSB BB1428, 1959 NE Pacific Street, Seattle, WA 98195-6540, USA
3 Department of Physiology and Biophysics, University of Washington School of Medicine, Box 356540, HSB BB1428, 1959 NE Pacific Street, Seattle, WA 98195-6540, USA
* Corresponding author. Tel: +1 781 744 8962. E-mail address: richard.w.nesto{at}lahey.org
The endocannabinoid system (ECS) is an endogenous signalling system involved in maintaining energy balance. The ECS works both centrally and peripherally to promote metabolic processes that can lead to weight gain, and recent investigations suggest that obesity may be associated with ECS overactivity. Obesity, in particular, abdominal obesity, is recognized as having a role in potentiating cardiometabolic risk factors and disease progression and is often overlooked as a risk factor requiring early monitoring and management. Adipose tissue is a very metabolically active endocrine organ secreting numerous bioactive molecules, adipocytokines, which can act locally and distally. In the obese state, with the notable exception of adiponectin, these cytokines are released in excess and lead to negative metabolic sequelae, such as the potentiation of atherogenic dyslipidaemia, insulin resistance, and hypertension. Blockade of the cannabinoid type 1 (CB1) receptor with the CB1 receptor blocker, rimonabant, has been shown to reduce overall and abdominal obesity and improve a number of metabolic variables, including glucose tolerance, reduced plasma levels of triglycerides and insulin, and increased levels of high density lipoprotein (HDL) cholesterol and adiponectin. In addition, the pro-inflammatory and pro-atherogenic state is reduced, as evidenced by a reduction in the C-reactive protein and atherogenic ApoB lipoprotein, respectively. Thus, blockade of the CB1 receptor may potentially reduce abdominal obesity and some other associated cardiometabolic risk factors.
Key Words: Abdominal obesity • Endocannabinoid • Global cardiometabolic risk • Rimonabant • Type 2 diabetes