title: Imaging mass spectrometry demonstrates age-related decline in human adipose plasticity.
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.
authors.affiliation: 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.
authors.forename: Christelle
authors.initials: C
authors.lastname: Guillermier
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.|Department of Medicine, Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Pouneh K
authors.initials: PK
authors.lastname: Fazeli
authors.affiliation: Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Soomin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Lun
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jonah P
authors.initials: JP
authors.lastname: Zuflacht
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Milian
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.|Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.affiliation: CAMECA, Madison, Wisconsin, USA.
authors.forename: Hugues
authors.initials: H
authors.lastname: Francois-Saint-Cyr
authors.affiliation: CAMECA, Gennevilliers, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Horreard
authors.affiliation: CAMECA, Madison, Wisconsin, USA.
authors.forename: David
authors.initials: D
authors.lastname: Larson
authors.affiliation: 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.
authors.forename: Evan D
authors.initials: ED
authors.lastname: Rosen
authors.affiliation: 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.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Claude P
authors.initials: CP
authors.lastname: Lechene
authors.affiliation: 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.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Steinhauser
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis; D000328:Adult; D000375:Aging / Q000502:physiology*; D005260:Female; D006706:Homeostasis; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged; D013347:Subcellular Fractions / Q000378:metabolism; D050151:Subcutaneous Fat / Q000166:cytology* / Q000378:metabolism*
chemical_list: C583557:IGF1 protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I