Journal
FRONTIERS IN PHARMACOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.594574
Keywords
obesity; non-alcoholic fatty liver disease; ketone; ketosis; apolipoprotein; heme oxygenase; HO-1
Categories
Funding
- National Institutes of Health [1R01DK121797-01A1, 1R01DK126884-01]
- National Heart, Lung and Blood Institute [K01HL125445, P01 HL05197-11]
- National Institute of General Medical Sciences [P20GM104357-02]
- National Institute of General Medical Sciences (NIGMS) a component of the National Institutes of Health (NIH) as one of its Centers of Biomedical Research Excellence (COBRE) [P30GM122733]
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The inverse relationship of plasma bilirubin levels with liver fat accumulation has prompted the possibility of bilirubin as a therapeutic for non-alcoholic fatty liver disease. Here, we used diet-induced obese mice with non-alcoholic fatty liver disease treated with pegylated bilirubin (bilirubin nanoparticles) or vehicle control to determine the impact on hepatic lipid accumulation. The bilirubin nanoparticles significantly reduced hepatic fat, triglyceride accumulation, de novo lipogenesis, and serum levels of liver dysfunction marker aspartate transaminase and ApoB100 containing very-low-density lipoprotein. The bilirubin nanoparticles improved liver function and activated the hepatic beta-oxidation pathway by increasing PPAR alpha and acyl-coenzyme A oxidase 1. The bilirubin nanoparticles also significantly elevated plasma levels of the ketone beta-hydroxybutyrate and lowered liver fat accumulation. This study demonstrates that bilirubin nanoparticles induce hepatic fat utilization, raise plasma ketones, and reduce hepatic steatosis, opening new therapeutic avenues for NAFLD.
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