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

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Science Translational Medicine  03 Oct 2018:
Vol. 10, Issue 461, eaar2680
DOI: 10.1126/scitranslmed.aar2680

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Enlightening endolysosomal lipids

Lipid accumulation contributes to multiple diseases including atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and lysosomal storage diseases. To noninvasively measure lipids in vivo, Galassi et al. engineered a carbon nanotube optical reporter for endolysosomal organelle uptake. In mouse models of lysosomal storage disease and NAFLD, the nanoreporter’s near-infrared fluorescence tracked lipid accumulation within Kupffer cells (liver macrophages) and revealed that switching mice from a high-fat, high-fructose diet to standard chow only partially reversed liver lipid accumulation. This optical imaging agent could help to elucidate mechanisms of lipid accumulation in disease or be useful for drug development testing.

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.

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