Curcumin analogues as selective fluorescence imaging probes for brown adipose tissue and monitoring browning.
Manipulation of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can be promising new approaches to counter metabolic disorder diseases in humans. Imaging probes that could consistently monitor BAT mass and browning of WAT are highly desirable. In the course of our imaging probe screening, we found that BAT could be imaged with curcumin analogues in mice. However, the poor BAT selectivity over WAT and short emissions of the lead probes promoted further lead optimization. Limited uptake mechanism studies suggested that CD36/FAT (fatty acid transporter) probably contributed to the facilitated uptake of the probes. By increasing the stereo-hindrance of the lead compound, we designed CRANAD-29 to extend the emission and increase the facilitated uptake, thus increasing its BAT selectivity. Our data demonstrated that CRANAD-29 had significantly improved selectivity for BAT over WAT, and could be used for imaging BAT mass change in a streptozotocin-induced diabetic mouse model, as well as for monitoring BAT activation under cold exposure. In addition, CRANAD-29 could be used for monitoring the browning of subcutaneous WAT (sWAT) induced by β3-adrenoceptor agonist CL-316, 243.
1] Molecular Imaging Laboratory, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA [2] School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China [3] Department of pharmacy, ZhongDa Hospital, Southeast University, Nanjing 210009, China.
Xueli
X
Zhang
1] Molecular Imaging Laboratory, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA [2] Department of Parasitology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Yanli
Y
Tian
Joslin Diabetes Center, Harvard Medical School, and Harvard Stem Cell Institute, Boston, MA 02215.
Hongbin
H
Zhang
Molecular Imaging Laboratory, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
Amol
A
Kavishwar
Joslin Diabetes Center, Harvard Medical School, and Harvard Stem Cell Institute, Boston, MA 02215.
Matthew
M
Lynes
Molecular Imaging Laboratory, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
Anna-Liisa
AL
Brownell
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Hongbin
H
Sun
Joslin Diabetes Center, Harvard Medical School, and Harvard Stem Cell Institute, Boston, MA 02215.
Yu-Hua
YH
Tseng
Molecular Imaging Laboratory, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
Anna
A
Moore
Molecular Imaging Laboratory, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
Chongzhao
C
Ran
D041721:3T3-L1 Cells; D002001:Adipose Tissue, Brown / Q000502:physiology*; D052436:Adipose Tissue, White / Q000502:physiology; D000818:Animals; D003474:Curcumin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D013194:Staining and Labeling; D051598:Whole Body Imaging
D005456:Fluorescent Dyes; D003474:Curcumin