In Vivo Imaging of Lipid Droplets and Oxygen Status in Hepatic Tissues of Nonalcoholic Fatty Liver Model Mice Using a Lipophilic Ir(III) Complex.
Anal Chem
; 95(7): 3729-3735, 2023 02 21.
Article
en En
| MEDLINE
| ID: mdl-36759196
Nonalcoholic fatty liver disease (NAFLD) is becoming common worldwide. In pathophysiological studies of NAFLD, an in vivo optical probe that enables visualization of lipid droplets (LDs) and imaging of oxygen status in hepatic tissues simultaneously would be very useful. Here, we present the phosphorescent Ir(III) complex BTP ((btp)2Ir(acac) (btp = benzothienylpyridine, acac = acetylacetone)) as the first probe that meets this requirement. BTP was efficiently taken up into cultured 3T3-L1 adipocytes and selectively accumulated into LDs. Quantifying oxygen levels in LDs based on the phosphorescence lifetime of BTP allowed us to track changes in cellular oxygen tension after treatment with metabolic stimulants. Phosphorescence lifetime imaging microscopy combined with intravenously administered BTP in mice enabled specific visualization of LDs in hepatic lobules and simultaneous imaging of the oxygen gradient that decreased from the portal vein (PV) to the central vein (CV). NAFL model mice were created by feeding a high-fat diet (HFD) to mice for 3 or 7 days. The mice fed an HFD showed a marked increase in the amount and size of LDs in hepatocytes compared with those fed a normal diet, leading to abnormal microvascular structures. In addition, HFD-fed mice also exhibited reduced oxygen tension in areas other than the CV. Multicolor imaging with the LD-accumulated oxygen probe BTP and vasculature-staining FITC-lectin suggested that structural distortions of the sinusoidal microvasculature caused by enlarged LDs were associated with partial hypoxia in NAFL.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad del Hígado Graso no Alcohólico
Límite:
Animals
Idioma:
En
Revista:
Anal Chem
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos