An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo.

Abstract

The abnormal accumulation of lipids within the endolysosomal lumen occurs in many conditions, including lysosomal storage disorders, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and drug-induced phospholipidosis. Current methods cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug development and research into the mechanisms linking endolysosomal lipid accumulation to disease progression. We developed a single-walled carbon nanotube-based optical reporter that noninvasively measures endolysosomal lipid accumulation via bandgap modulation of its intrinsic near-infrared emission. The reporter detected lipid accumulation in Niemann-Pick disease, atherosclerosis, and NAFLD models in vivo. By applying the reporter to the study of NAFLD, we found that elevated lipid quantities in hepatic macrophages caused by a high-fat diet persist long after reverting to a normal diet. The reporter dynamically monitored endolysosomal lipid accumulation in vivo over time scales ranging from minutes to weeks, indicating its potential to accelerate preclinical research and drug development processes.

• Authors: Thomas V Galassi, Prakrit V Jena, Janki Shah, Geyou Ao, Elizabeth Molitor, Yaron Bram, Angela Frankel, Jiwoon Park, Jose Jessurun, Daniel S Ory, Adriana Haimovitz-Friedman, Daniel Roxbury, Jeetain Mittal, Ming Zheng, Robert E Schwartz, Daniel A Heller
• Journal: Science translational medicine (Sci Transl Med) Vol. 10 Issue 461 (10 03 2018) ISSN: 1946-6242 [Electronic] United States
• PMID: 30282694 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Lipoproteins, LDL
• oxidized low density lipoprotein

Topics

• Animals
• Cell Survival
• Diet
• Disease Models, Animal
• Endosomes (metabolism)
• Gene Expression Regulation
• Lipid Metabolism
• Lipoproteins, LDL (metabolism)
• Liver (cytology)
• Lysosomal Storage Diseases (diagnosis, metabolism)
• Lysosomes (metabolism)
• Macrophages (metabolism)
• Male
• Mice, Inbred C57BL
• Nanoparticles (chemistry)
• Non-alcoholic Fatty Liver Disease (blood, genetics, pathology)
• Optical Imaging
• Tissue Distribution