The role of cannabinoid receptor type-1 in metabolic endotoxemia-induced metabolic dysfunctions
Grunewald, Zachary Ian
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Obesity is characterized by inflammation and insulin resistance. Lipopolysaccharide (LPS) derived from Gram-negative gut bacteria increases with obesity (metabolic endotoxemia) and has been identified as a triggering factor for the development of obesity-associated inflammation and insulin resistance. Additionally, LPS has been shown to regulate endocannabinoid synthesis and endocannabinoid system tone. Our research used a pair-fed rat model to determine the role of cannabinoid receptor type-1 (CB1) in metabolic endotoxemia-induced inflammation, insulin resistance, insulin clearance, and atherogenesis. We found that metabolic endotoxemia induced inflammation, insulin resistance, and increased hepatic insulin clearance. Furthermore, CB1 inhibition partially restored the metabolic alterations induced by low level LPS exposure. In conclusion, our findings suggest that metabolic endotoxemia partially acts through CB1 to induce metabolic dysfunctions.