Gadofullerene inhibits the degradation of apolipoprotein B100 and boosts triglyceride transport for reversing hepatic steatosis
Open Access
- 1 September 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (37), eabc1586
- https://doi.org/10.1126/sciadv.abc1586
Abstract
Hepatic steatosis is a widespread metabolic disease characterized by excessive accumulation of triglyceride (TG) in liver. So far, effective approved drugs for hepatic steatosis are still in development, and removing the unnecessary TG from the hepatocytes is an enormous challenge. Here, we explore a promising anti-hepatic steatosis strategy by boosting hepatocellular TG transport using.-alanine-modified gadofullerene (GF-Ala) nanoparticles. We confirm that GF-Ala could reverse hepatic steatosis in oleic acid-induced hepatocytes, fructose-induced mice, and obesity-associated transgenic ob/ob mice. Observably, GF-Ala improves hepatomegaly and hepatic lipid accumulation, reduces lipid peroxidation, and repairs abnormal mitochondria. Of note, we demonstrate that GF-Ala markedly inhibits the posttranslational degradation of apolipoprotein B100 (ApoB100) and boosts hepatocellular TG transport based on their superior antioxidant property. Together, we conclude that GF-Ala could potently ameliorate hepatic TG transport and maintain hepatic metabolic homeostasis without apparent toxicity, being beneficial for treatments of hepatic steatosis and other fatty liver diseases.This publication has 38 references indexed in Scilit:
- Nuclear receptor PPARγ-regulated monoacylglycerol O -acyltransferase 1 (MGAT1) expression is responsible for the lipid accumulation in diet-induced hepatic steatosisProceedings of the National Academy of Sciences of the United States of America, 2012
- The inhibition of death receptor mediated apoptosis through lysosome stabilization following internalization of carboxyfullerene nanoparticlesBiomaterials, 2011
- Human Fatty Liver Disease: Old Questions and New InsightsScience, 2011
- Pioglitazone, Vitamin E, or Placebo for Nonalcoholic SteatohepatitisThe New England Journal of Medicine, 2010
- Fullerene Nanoparticles Selectively Enter Oxidation-Damaged Cerebral Microvessel Endothelial Cells and Inhibit JNK-Related ApoptosisACS Nano, 2009
- The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materialsBiomaterials, 2008
- Reduction of hepatic steatosis in rats and mice after treatment with a liver-targeted thyroid hormone receptor agonistHepatology, 2008
- Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality controlProceedings of the National Academy of Sciences of the United States of America, 2008
- Activation of Peroxisome Proliferator–Activated Receptor (PPAR)δ Promotes Reversal of Multiple Metabolic Abnormalities, Reduces Oxidative Stress, and Increases Fatty Acid Oxidation in Moderately Obese MenDiabetes, 2008
- A human hepatocellular in vitro model to investigate steatosisChemico-Biological Interactions, 2007