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.
Christelle Guillermier, Pouneh K. Fazeli, Soomin Kim, Mingyue Lun, Jonah P. Zuflacht, Jessica Milian, Hang Lee, Hugues Francois-Saint-Cyr, Francois Horreard, David Larson, Evan D. Rosen, Richard T. Lee, Claude P. Lechene, Matthew L. Steinhauser
Title and authors | Publication | Year |
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Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients
Tongu Y, Kasahara T, Akiyama Y, Suzuki T, Ho HJ, Matsumoto Y, Kujirai R, Kikuchi K, Nata K, Kanzaki M, Suzuki K, Watanabe S, Kawabe C, Miyata Y, Itai S, Toyohara T, Suzuki C, Tanaka T, Wada J, Tomioka Y, Abe T |
Scientific Reports | 2025 |
The role of adipogenic niche resident cells in colorectal cancer progression in relation to obesity
Domagalski M, Olszańska J, Pietraszek\u2010Gremplewicz K, Nowak D |
Obesity Reviews | 2025 |
Exercise Alleviates Aging of Adipose Tissue through Adipokine Regulation
Jia D, Zhang H, Liu T, Wang R |
Metabolites | 2024 |
Lactate transport inhibition therapeutically reprograms fibroblast metabolism in experimental pulmonary fibrosis.
Ziehr DR, Li F, Parnell KM, Krah NM, Leahy KJ, Guillermier C, Varon J, Baron RM, Maron BA, Philp NJ, Hariri LP, Kim EY, Steinhauser ML, Knipe RS, Rutter J, Oldham WM |
bioRxiv : the preprint server for biology | 2024 |
Nanoscale imaging of DNA-RNA identifies transcriptional plasticity at heterochromatin
Guillermier C, Kumar NV, Bracken RC, Alvarez D, O\u2019Keefe J, Gurkar A, Brown JD, Steinhauser ML |
Life Science Alliance | 2024 |
Exceptional longevity of mammalian ovarian and oocyte macromolecules throughout the reproductive lifespan.
Bomba-Warczak EK, Velez KM, Zhou LT, Guillermier C, Edassery S, Steinhauser ML, Savas JN, Duncan FE |
eLife | 2024 |
Viewing Pulmonary Arterial Hypertension Pathogenesis and Opportunities for Disease-Modifying Therapy Through the Lens of Biomass.
Steinhauser ML, Maron BA |
JACC. Basic to translational science | 2024 |
Proline and glucose metabolic reprogramming supports vascular endothelial and medial biomass in pulmonary arterial hypertension
Bradley M. Wertheim, Rui-Sheng Wang, Christelle Guillermier, Christiane Hütter, William M. Oldham, Jörg Menche, Matthew Steinhauser, Bradley Maron |
JCI Insight | 2023 |
Using mass spectrometry imaging to visualize age-related subcellular disruption
Hogan KA, Zeidler JD, Beasley HK, Alsaadi AI, Alshaheeb AA, Chang YC, Tian H, Hinton AO Jr, McReynolds MR |
Frontiers in Molecular Biosciences | 2023 |
Extract of Isatidis Radix Inhibits Lipid Accumulation in In Vitro and In Vivo by Regulating Oxidative Stress
Han YH, Kee JY |
Antioxidants | 2023 |
The Roles of Lipid Metabolism in the Pathogenesis of Chronic Diseases in the Elderly
Song R, Hu M, Qin X, Qiu L, Wang P, Zhang X, Liu R, Wang X |
Nutrients | 2023 |
Adipose Tissue Dynamics: Cellular and Lipid Turnover in Health and Disease
Palacios-Marin I, Serra D, Jimenez-Chillarón J, Herrero L, Todorčević M |
Nutrients | 2023 |
Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry
Roeder SS, Bonnin EA, Wu TD, Guerquin-Kern JL, Jabari S, Brandner S, Eyüpoglu IY, Gollwitzer S, Hamer HM, Gerner ST, Döppner TR, Rummel C, Englund E, Heimke-Brinck R, Borst T, Daniel C, Amann K, Schlötzer-Schrehardt U, Tonchev AB, Roessler K, Schwab S, Bergmann O, Rizzoli SO, Huttner HB |
Frontiers in neuroscience | 2023 |
Exceptional longevity of mammalian ovarian and oocyte macromolecules throughout the reproductive lifespan
Bomba-Warczak EK, Velez KM, Zhou LT, Guillermier C, Edassery S, Steinhauser M, Savas JN, Duncan FE |
2023 | |
The Impact of Maternal Obesity on Adipose Progenitor Cells
Lecoutre S, Maqdasy S, Lambert M, Breton C |
Biomedicines | 2023 |
A Cycle of Inflammatory Adipocyte Death and Regeneration in Murine Adipose Tissue
A Monji, Y Zhang, G Kumar, C Guillermier, S Kim, B Olenchock, M Steinhauser |
Diabetes | 2022 |
Improvement of Pancreatic Steatosis and Indices of Insulin Resistance After Metabolic Surgery
Salman AA, Salman MA, Said M, El Sherbiny M, Elkassar H, Hassan MB, Marwan A, Morad MA, Ashoush O, Labib S, Aon MH, Awad A, Sayed M, Taha AE, Moustafa A, Shaaban HE, Khater A, Elewa A, Khalaf AM, Mostafa AA, Matter M, Youssef A |
Frontiers in Medicine | 2022 |
Importance of the Microenvironment and Mechanosensing in Adipose Tissue Biology
Lecoutre S, Lambert M, Drygalski K, Dugail I, Maqdasy S, Hautefeuille M, Clément K |
Cells | 2022 |
Research Progress in the Medical Application of Heavy Water, Especially in the Field of D2O-Raman Spectroscopy
Wang X, Liu NM, Zhao YF, Yang F, Zhu ZJ, Song D |
International journal of medical sciences | 2022 |
Dipeptidyl peptidase-4 cell surface expression marks an abundant adipose stem/progenitor cell population with high stemness in human white adipose tissue
Hatzmann FM, Großmann S, Waldegger P, Wiegers GJ, Mandl M, Rauchenwald T, Pierer G, Zwerschke W |
Adipocyte | 2022 |
Reviews on New Drug Targets in Age-Related Disorders: Part II
PC Guest |
2021 | |
Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics
P Morigny, J Boucher, P Arner, D Langin |
Nature Reviews Endocrinology | 2021 |
Aging adipose: Depot location dictates age-associated expansion and dysfunction
HV Bank, C Kirsh, J Simcox |
Ageing Research Reviews | 2021 |
Use of stable isotope-tagged thymidine and multi-isotope imaging mass spectrometry (MIMS) for quantification of human cardiomyocyte division
JW Yester, H Liu, F Gyngard, N Ammanamanchi, KC Little, D Thomas, ML Sullivan, S Lal, ML Steinhauser, B Kühn |
Nature Protocols | 2021 |
Recent advances in nucleotide analogue-based techniques for tracking dividing stem cells: an overview
GM Solius, DI Maltsev, VV Belousov, OV Podgorny |
The Journal of biological chemistry | 2021 |
Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1−/CD34+/CD24+ Adipose Stem/Progenitor Cells
FM Hatzmann, A Ejaz, GJ Wiegers, M Mandl, C Brucker, S Lechner, T Rauchenwald, M Zwierzina, S Baumgarten, S Wagner, M Mattesich, P Waldegger, G Pierer, W Zwerschke |
Cells | 2021 |
Design and rationale of a clinical trial to increase cardiomyocyte division in infants with tetralogy of Fallot
SR Khoudary, A Fabio, JW Yester, ML Steinhauser, AB Christopher, F Gyngard, PS Adams, VO Morell, M Viegas, JP Silva, LF Silva, M Castro-Medina, A McCormick, M Reyes-Múgica, M Barlas, H Liu, D Thomas, N Ammanamanchi, R Sada, M Cuda, E Hartigan, DK Groscost, B Kühn |
International Journal of Cardiology | 2021 |
Prolonged fasting drives a program of metabolic inflammation in human adipose tissue
PK Fazeli, Y Zhang, J O'Keefe, T Pesaresi, M Lun, B Lawney, ML Steinhauser |
Molecular Metabolism | 2020 |
Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease
A Chait, LJ den Hartigh |
Frontiers in Cardiovascular Medicine | 2020 |
Imaging Mass Spectrometry Reveals Tumor Metabolic Heterogeneity
Y Zhang, C Guillermier, TD Raedt, AG Cox, O Maertens, D Yimlamai, M Lun, A Whitney, RL Maas, W Goessling, K Cichowski, ML Steinhauser |
iScience | 2020 |
Metabolic Analysis at the Nanoscale with Multi‐Isotope Imaging Mass Spectrometry (MIMS)
DP Narendra, ML Steinhauser |
Current protocols in cell biology / editorial board, Juan S. Bonifacino ... [et al.] | 2020 |
Sprouty1 Prevents Cellular Senescence Maintaining Proliferation and Differentiation Capacity of Human Adipose Stem/Progenitor Cells
M Mandl, SA Wagner, FM Hatzmann, A Ejaz, H Ritthammer, S Baumgarten, HP Viertler, J Springer, ME Zwierzina, M Mattesich, C Brucker, P Waldegger, G Pierer, W Zwerschke, DL Couteur |
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences | 2020 |
CRISPR/Cas9-mediated gene knockout in human adipose stem/progenitor cells
M Mandl, H Ritthammer, A Ejaz, SA Wagner, FM Hatzmann, S Baumgarten, HP Viertler, ME Zwierzina, M Mattesich, V Schiller, T Rauchenwald, C Ploner, P Waldegger, G Pierer, W Zwerschke |
Adipocyte | 2020 |
Multi-isotope imaging mass spectrometry reveals heterogeneity of cell proliferation and glucose utilization in atherosclerotic plaques
Christelle Guillermier, Sean P. Doherty, Adam G. Whitney, Vladimir Babaev, MacRae Fort Linton, Matthew L. Steinhauser, Jonathan D. Brown |
JCI Insight | 2019 |
Reduced subcutaneous adipogenesis in human hypertrophic obesity is linked to senescent precursor cells
B Gustafson, A Nerstedt, U Smith |
Nature Communications | 2019 |
Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications
M Longo, F Zatterale, J Naderi, L Parrillo, P Formisano, GA Raciti, F Beguinot, C Miele |
International journal of molecular sciences | 2019 |
FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements
T van Zutphen, JH Stroeve, J Yang, VW Bloks, A Jurdzinski, H Roelofsen, NC Huijkman, TH van Dijk, RJ Vonk, J van Deursen, B Staels, AK Groen, F Kuipers |
Journal of lipid research | 2019 |
Dietary calories and lipids synergistically shape adipose tissue cellularity during postnatal growth
I Meln, G Wolff, T Gajek, J Koddebusch, S Lerch, L Harbrecht, W Hong, I Bayindir-Buchhalter, D Krunic, HG Augustin, A Vegiopoulos |
Molecular Metabolism | 2019 |
Biological explorations with nanoscale secondary ion mass spectrometry
F Gyngard, ML Steinhauser |
Journal of Analytical Atomic Spectrometry | 2019 |
Targeting nuclear receptor NR4A1-dependent adipocyte progenitor quiescence promotes metabolic adaptation to obesity
Yang Zhang, Alexander J Federation, Soomin Kim, John O'Keefe, Mingyue Lun, Dongxi Xiang, Jonathan D. Brown, Matthew L. Steinhauser |
Journal of Clinical Investigation | 2018 |
Optical imaging of metabolic dynamics in animals
L Shi, C Zheng, Y Shen, Z Chen, ES Silveira, L Zhang, M Wei, C Liu, C de Sena-Tomas, K Targoff, W Min |
Nature Communications | 2018 |
Amyloid-β Plaques in Clinical Alzheimer’s Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity
NC Wildburger, F Gyngard, C Guillermier, BW Patterson, D Elbert, KG Mawuenyega, T Schneider, K Green, R Roth, RE Schmidt, NJ Cairns, TL Benzinger, ML Steinhauser, RJ Bateman |
Frontiers in neurology | 2018 |
Quantitative imaging of deuterated metabolic tracers in biological tissues with nanoscale secondary ion mass spectrometry
C Guillermier, JC Poczatek, WR Taylor, ML Steinhauser |
International Journal of Mass Spectrometry | 2017 |
Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights
AR Buchberger, K DeLaney, J Johnson, L Li |
Analytical Chemistry | 2017 |