Activation of cannabinoid receptor type 1 (Cb1r) disrupts hepatic insulin receptor signaling via cyclic AMP-response element-binding protein H (Crebh)-mediated induction of Lipin1 gene

Abstract

Background: The role of Cb1r signaling-mediated activation of Crebh in regulating lipid metabolism and insulin signaling is currently unknown. Results: Cb1r signaling regulates Lipin1 gene transcription via Crebh and inhibits insulin receptor signaling. Conclusion: Crebh-mediated activation of Lipin1 by Cb1r deregulates insulin receptor signaling. Significance: Relieving higher hepatic DAG levels by targeting its upstream regulators might be beneficial to restore insulin signaling.