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JCI Insight. 2017 Mar 9;2(5):e90349. doi: 10.1172/jci.insight.90349.

Imaging mass spectrometry demonstrates age-related decline in human adipose plasticity.

Author information

1
Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Center for NanoImaging, Brigham and Women's Hospital, Cambridge, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.
2
Harvard Medical School, Boston, Massachusetts, USA.; Department of Medicine, Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
3
Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.
4
Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
5
Harvard Medical School, Boston, Massachusetts, USA.; Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
6
CAMECA, Madison, Wisconsin, USA.
7
CAMECA, Gennevilliers, France.
8
Harvard Medical School, Boston, Massachusetts, USA.; Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
9
Harvard Medical School, Boston, Massachusetts, USA.; Department of Medicine, Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Harvard Stem Cell Institute and; Department of Stem Cell and Regenerative Medicine, Harvard University, Cambridge, Massachusetts, USA.
10
Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Center for NanoImaging, Brigham and Women's Hospital, Cambridge, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Harvard Stem Cell Institute and.

Abstract

Quantification of stable isotope tracers has revealed the dynamic state of living tissues. A new form of imaging mass spectrometry quantifies isotope ratios in domains much smaller than a cubic micron, enabling measurement of cell turnover and metabolism with stable isotope tracers at the single-cell level with a methodology we refer to as multi-isotope imaging mass spectrometry. In a first-in-human study, we utilize stable isotope tracers of DNA synthesis and de novo lipogenesis to prospectively measure cell birth and adipocyte lipid turnover. In a study of healthy adults, we elucidate an age-dependent decline in new adipocyte generation and adipocyte lipid turnover. A linear regression model suggests that the aging effect could be mediated by a decline in insulin-like growth factor-1 (IGF-1). This study therefore establishes a method for measurement of cell turnover and metabolism in humans with subcellular resolution while implicating the growth hormone/IGF-1 axis in adipose tissue aging.

Conflict of interest statement

Conflict of interest: H. Francois-Saint-Cyr, F. Horreard, and D. Larson are employed by CAMECA, which manufactures the NanoSIMS instrument.

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