The ECS is upregulated in the brain, liver, and adipose tissue in chronic obesity. In the brain, the hypothalamus plays a principal role in the control of feeding and regulation of body weight, and excessive cannabinoid expression in the hypothalamus is associated with obesity.
CB1-R stimulation leads to dopamine release in the nucleus accumbens shell, which increases motivation to eat. These effects result in increased food intake and fat accumulation.
In the peripheral arena, ECS overactivation promotes lipogenesis at the level of adipose tissue and the liver. ECS activity in the GI tract interferes with feelings of satiety, and CB1-R stimulation of skeletal muscle decreases glucose uptake. All of these central and peripheral effects contribute to the increased risk of dyslipidemia, insulin resistance, glucose intolerance and increased cardiometabolic risk.
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