Abstract
Studies have indicated that increasing plasma bilirubin levels might be useful for preventing and treating hepatic lipid accumulation that occurs with metabolic diseases such as obesity and diabetes. We have previously demonstrated that mice with hyperbilirubinemia had significantly less lipid accumulation in a diet-induced non-alcoholic fatty liver disease (NAFLD) model. However, bilirubin’s effects on individual lipid species are currently unknown. Therefore, we used liquid chromatography-mass spectroscopy (LC-MS) to determine the hepatic lipid composition of obese mice with NAFLD treated with bilirubin nanoparticles or vehicle control. We placed the mice on a high-fat diet (HFD) for 24 weeks and then treated them with bilirubin nanoparticles or vehicle control for 4 weeks while maintaining the HFD. Bilirubin nanoparticles suppressed hepatic fat content overall. After analyzing the lipidomics data, we determined that bilirubin inhibited the accumulation of ceramides in the liver. The bilirubin nanoparticles significantly lowered the hepatic expression of two essential enzymes that regulate ceramide production, Sgpl1 and Degs1. Our results demonstrate that the bilirubin nanoparticles improve hepatic fat content by reducing ceramide production, remodeling the liver fat content, and improving overall metabolic health.
Document Type
Article
Publication Date
2-2023
Digital Object Identifier (DOI)
https://doi.org/10.3390/metabo13020215
Funding Information
This work was supported by the National Institutes of Health R01DK121797 (T.D.H.J.) and R01DK126884 (D.E.S.), the National Heart, Lung, and Blood Institute K01HL125445 (T.D.H.J.) and P01 HL0519711 (D.E.S.), and the National Institute of General Medical Sciences P20GM104357 (D.E.S.). The lipidomics analysis was supported by the COBRE grant (P30GM127211) at the University of Kentucky. Research reported in this study was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institute of Health under grant number P30 GM127211. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Repository Citation
Kipp, Zachary A.; Martinez, Genesee J.; Bates, Evelyn A.; Maharramov, Agil B.; Flight, Robert M.; Moseley, Hunter N. B.; Morris, Andrew J.; Stec, David E.; and Hinds, Terry D. Jr., "Bilirubin Nanoparticle Treatment in Obese Mice Inhibits Hepatic Ceramide Production and Remodels Liver Fat Content" (2023). Markey Cancer Center Faculty Publications. 305.
https://uknowledge.uky.edu/markey_facpub/305
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Notes/Citation Information
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).