A System for In Vivo Imaging of Hepatic Free Fatty Acid Uptake

Gastroenterology. 2017 Jan;152(1):78-81.e2. doi: 10.1053/j.gastro.2016.10.002. Epub 2016 Oct 11.

Abstract

Alterations in hepatic free fatty acid (FFA) uptake and metabolism contribute to the development of prevalent liver disorders such as hepatosteatosis. However, detecting dynamic changes in FFA uptake by the liver in live model organisms has proven difficult. To enable noninvasive real-time imaging of FFA flux in the liver, we generated transgenic mice with liver-specific expression of luciferase and performed bioluminescence imaging with an FFA probe. Our approach enabled us to observe the changes in FFA hepatic uptake under different physiological conditions in live animals. By using this method, we detected a decrease in FFA accumulation in the liver after mice were given injections of deoxycholic acid and an increase after they were fed fenofibrate. In addition, we observed diurnal regulation of FFA hepatic uptake in living mice. Our imaging system appears to be a useful and reliable tool for studying the dynamic changes in hepatic FFA flux in models of liver disease.

Keywords: Lipid; Metabolism; Mouse Model; Visualization.

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Cholagogues and Choleretics / pharmacology
  • Circadian Rhythm
  • Deoxycholic Acid / pharmacology
  • Fatty Acids / metabolism*
  • Fenofibrate / pharmacology
  • Hypolipidemic Agents / pharmacology
  • Liver / diagnostic imaging*
  • Liver / metabolism*
  • Luciferases / genetics
  • Luminescent Measurements*
  • Male
  • Mice
  • Mice, Transgenic
  • Photography

Substances

  • Cholagogues and Choleretics
  • Fatty Acids
  • Hypolipidemic Agents
  • Deoxycholic Acid
  • Luciferases
  • Fenofibrate