Metabolic syndrome is a complex disease state, which appears mostly as a consequence
of an unhealthy, sedentary lifestyle. Metabolic complications include insulin resistance
(IR), diabetes, dyslipidemia, hypertension, and atherosclerosis, impairing life standards
and reducing life expectancy. The endocannabinoid system (ECS) has an important role
in signalization processes, not only in the central nervous system, but also in the
peripheral tissues. Several physiological functions are affected, and overexpression
or downregulation contributes to several diseases. A better understanding of the functions
of cannabinoid (CB) receptors may propose potential therapeutic effects by influencing
receptor signaling and enzymes involved in downstream pathways. In this review, we
summarize recent information regarding the roles of the ECS and the CB1 receptor signaling
in the physiology and pathophysiology of energy and metabolic homeostasis, in the
development of obesity by enhancing food intake, upregulating energy balance and fat
accumulation, increasing lipogenesis and glucose production, and impairing insulin
sensitivity and secretion. By analyzing the roles of the ECS in physiological and
pathophysiological mechanisms, we introduce some recently identified signaling pathways
in the mechanism of the pathogenesis of metabolic syndrome. Our review emphasizes
that the presence of such recently identified ECS signaling steps raises new therapeutic
potential in the treatment of complex metabolic diseases such as diabetes, insulin
resistance, obesity, and hypertension.
