Reversal of diet-induced hepatic steatosis by peripheral CB1 receptor blockade in mice is p53/miRNA-22/SIRT1/PPARα dependent.

ABSTRACT:

Objective

The endocannabinoid (eCB) system is increasingly recognized as being crucially important in obesity-related hepatic steatosis. By activating the hepatic cannabinoid-1 receptor (CB₁R), eCBs modulate lipogenesis and fatty acid oxidation. However, the underlying molecular mechanisms are largely unknown.

Methods

We combined unbiased bioinformatics techniques, mouse genetic manipulations, multiple pharmacological, molecular, and cellular biology approaches, and genomic sequencing to systematically decipher the role of the hepatic CB₁R in modulating fat utilization in the liver and explored the downstream molecular mechanisms.

Results

Using an unbiased normalized phylogenetic profiling analysis, we found that the CB₁R evolutionaril

SUBMITTER: Azar S 

PROVIDER: S-EPMC7563015 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature