The role of beta 1 adrenergic receptor in Non-Alcoholic Fat Liver Disease development

Abstract

Non-Alcoholic Fat Liver Disease (NAFLD) is characterized by the development of macrovesicular steatosis in the absence of significant consumption of alcohol, which can progress to nonalcoholic steato-hepatitis (NASH). Knockout mice for the β1 adrenergic receptor (β1KO) are obese when placed on high fat diet (HFD) and develop NASH with severe steatosis and fibrosis. The aim of this study was to determine if β1 adrenergic receptors have a direct role in NASH development or if this abnormality is due to the severe obesity observed in these mice. For that we analyzed genes related to lipid metabolism in the liver of obese β1KO. Fatty acids, triglycerides and cholesterol synthesis were increased in β1KO HFD (ChREBP: 5.55±0.2 vs. 2.28±0.04 WT, p<0.05; SREBP1c: 2.52±0.4 vs. 1.32±0.02 WT, p<0.05; DGAT2: 2±0.3 vs. 1.3±0.1 WT, p<0.05; SREBP2: 3.22±0.5 vs. 0.67±0.06 WT, p<0.05) resulting in hepatic triglycerides accumulation whereas hepatic secretion of lipoproteins were decreased (MTTP: 0.32±0.01 vs. 0.6±0.03 WT, p<0.05). These data showed an imbalance in lipoproteins synthesis and export, resulting in NASH. In conclusion, β1 adrenergic receptor has a direct influence on expression of genes related to lipid metabolism, and its absence leads to NASH when mice are treated with HFD.