Endocannabinoid System Mediation
In biological terms, the association between MS and increased cardiovascular risk seems to be mediated by the endocannabinoid system (ECS). The mechanism functions through binding of endocannabinoids at the cannabinoid receptors (CB1), which regulate appetite and energy homeostasis, emotions such as anxiety and fear, and behaviors such as food and water intake. CB1 receptors are also found in peripheral tissues such as liver, pancreas, skeletal muscle and adipose tissues, where they play an important role in lipid and glucose metabolism. Metabolic alterations such as dyslipidemia, insulin resistance, lipogenesis, excessive weight gain and increasing intra-abdominal obesity have been associated with overactivation of the ECS. Recent data suggest that the ECS is overactivated in the presence of abdominal obesity and/or diabetes, which contributes to further disturbances of energy balance and metabolism. In addition to regulating the intake of nutrients through central mechanisms located within the hypothalamus and limbic area, the ECS also intervenes in transport, metabolism and deposition of nutrients in the digestive tract, liver, adipose tissue, skeletal muscle and possibly the pancreas. Thus, activation of both central and peripheral CB1 receptors promotes weight gain and associated metabolic changes.
Recently, the medical community has shown great interest in the CB1 receptor antagonists, which were expected to advance the treatment of obesity and MS. This class of drugs has been shown to reduce bodyweight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels and to increase HDL-cholesterol and adiponectin concentrations in both nondiabetic and diabetic overweight/obese patients. However, rimonabant, the first clinically available member of this class of drugs, has been linked to an increased risk of anxiety, depression and suicidality, and was thus withdrawn from the market in 2008.
In behavioral terms, psychological conditions closely related to chronic stress, such as anxiety and depression, can lead to overeating, co-elevation of cortisol and insulin levels, and suppression of certain anabolic hormones. This state of metabolic stress, in turn, promotes abdominal adiposity. This biochemical environment appears to be conducive to several cell aging mechanisms and to influence a variety of diseases through a biochemical cascade leading to immune cell senescence.
Expert Rev Endocrinol Metab. 2012;7(1):63-71. © 2012 Expert Reviews Ltd.