Real-Time Noninvasive Imaging of Fatty Acid Uptake in Vivo

被引:56
作者
Henkin, Amy H. [1 ]
Cohen, Allison S. [2 ]
Dubikovskaya, Elena A. [2 ,5 ]
Park, Hyo Min [1 ]
Nikitin, Gennady F. [5 ]
Auzias, Mathieu G. [5 ]
Kazantzis, Melissa [1 ]
Bertozzi, Carolyn R. [2 ,3 ,4 ]
Stahl, Andreas [1 ]
机构
[1] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[4] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA
[5] Ecole Polytech Fed Lausanne, LCBIM, Inst Chem Sci & Engn, CH-1015 Lausanne, Switzerland
基金
美国国家卫生研究院;
关键词
TRANSPORT PROTEIN-1; LIVING SUBJECTS; ABSORPTION; EXPRESSION; RESISTANCE; SUBSTRATE; CLEAVAGE; DISEASE; OBESITY; CLONING;
D O I
10.1021/cb300194b
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Detection and quantification of fatty acid fluxes in animal model systems following physiological, pathological, or pharmacological challenges is key to our understanding of complex metabolic networks as these macronutrients also activate transcription factors and modulate signaling cascades including insulin sensitivity. To enable noninvasive, real-time, spatiotemporal quantitative imaging of fatty acid fluxes in animals, we created a bioactivatable molecular imaging probe based on long chain fatty acids conjugated to a reporter molecule (luciferin). We show that this probe faithfully recapitulates cellular fatty acid uptake and can be used in animal systems as a valuable tool to localize and quantitate in real time lipid fluxes such as intestinal fatty acid absorption and brown adipose tissue activation. This imaging approach should further our understanding of basic metabolic processes and pathological alterations in multiple disease models.
引用
收藏
页码:1884 / 1891
页数:8
相关论文
共 46 条
[1]   CLONING OF A RAB3 ISOTYPE PREDOMINATELY EXPRESSED IN ADIPOCYTES [J].
BALDINI, G ;
HOHL, T ;
LIN, HY ;
LODISH, HF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (11) :5049-5052
[2]   Free fatty acids in obesity and type 2 diabetes:: defining their role in the development of insulin resistance and β-cell dysfunction [J].
Boden, G ;
Shulman, GI .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2002, 32 :14-23
[3]   Shifting foci of hematopoiesis during reconstitution from single stem cells [J].
Cao, YA ;
Wagers, AJ ;
Beilhack, A ;
Dusich, J ;
Bachmann, MH ;
Negrin, RS ;
Weissman, IL ;
Contag, CH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (01) :221-226
[4]   Metabolic remodeling associated with subchronic doxorubicin cardiomyopathy [J].
Carvalho, Rui A. ;
Sousa, Rui P. B. ;
Cadete, Virgilio J. J. ;
Lopaschuk, Gary D. ;
Palmeira, Carlos M. M. ;
Bjork, James A. ;
Wallace, Kendall B. .
TOXICOLOGY, 2010, 270 (2-3) :92-98
[5]   A novel mouse model of lipotoxic cardiomyopathy [J].
Chiu, HC ;
Kovacs, A ;
Ford, DA ;
Hsu, FF ;
Garcia, R ;
Herrero, P ;
Saffitz, JE ;
Schaffer, JE .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (07) :813-822
[6]   Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy [J].
Chiu, HC ;
Kovacs, A ;
Blanton, RM ;
Han, XL ;
Courtois, M ;
Weinheimer, CJ ;
Yamada, KA ;
Brunet, S ;
Xu, HD ;
Nerbonne, JM ;
Welch, MJ ;
Fettig, NM ;
Sharp, TL ;
Sambandam, N ;
Olson, KM ;
Ory, DS ;
Schaffer, JE .
CIRCULATION RESEARCH, 2005, 96 (02) :225-233
[7]   Synthesis and preliminary evaluation of 18F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation [J].
DeGrado, TR ;
Wang, SY ;
Holden, JE ;
Nickles, RJ ;
Taylor, M ;
Stone, CK .
NUCLEAR MEDICINE AND BIOLOGY, 2000, 27 (03) :221-231
[8]   SUBSTRATE-BINDING PROPERTIES OF FIREFLY LUCIFERASE .I. LUCIFERIN-BINDING SITE [J].
DENBURG, JL ;
LEE, RT ;
MCELROY, WD .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1969, 134 (02) :381-&
[9]   In Vivo Bioluminescence Imaging of Furin Activity in Breast Cancer Cells Using Bioluminogenic Substrates [J].
Dragulescu-Andrasi, Anca ;
Liang, Gaolin ;
Rao, Jianghong .
BIOCONJUGATE CHEMISTRY, 2009, 20 (08) :1660-1666
[10]   Aging and the intestine [J].
Drozdowski, Laurie ;
Thomson, Alan B. R. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2006, 12 (47) :7578-7584