Exercise training remodels inguinal white adipose tissue through adaptations in innervation, vascularization, and the extracellular matrix

Pasquale Nigro; Maria Vamvini; Jiekun Yang; Tiziana Caputo; Li Lun Ho; Nicholas P. Carbone; Danae Papadopoulos; Royce Conlin; Jie He; Michael F. Hirshman; Joseph D. White; Jacques Robidoux; Robert C. Hickner; Søren Nielsen; Bente K. Pedersen; Manolis Kellis; Roeland J.W. Middelbeek; Laurie J. Goodyear

doi:10.1016/j.celrep.2023.112392

Exercise training remodels inguinal white adipose tissue through adaptations in innervation, vascularization, and the extracellular matrix

Pasquale Nigro, Maria Vamvini, Jiekun Yang, Tiziana Caputo, Li Lun Ho, Nicholas P. Carbone, Danae Papadopoulos, Royce Conlin, Jie He, Michael F. Hirshman, Joseph D. White, Jacques Robidoux, Robert C. Hickner, Søren Nielsen, Bente K. Pedersen, Manolis Kellis, Roeland J.W. Middelbeek, Laurie J. Goodyear^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

19 Citations (Scopus)

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Abstract

Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood, and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses, we find that 11 days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition and increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism.

Original language	English
Article number	112392
Journal	Cell Reports
Volume	42
Issue number	4
Number of pages	22
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2023.112392
Publication status	Published - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

Adipo-Clear
CP: Metabolism
CP: Molecular biology
ECM
exercise
innervation
NEGR1
PRDM16
proteomics
spatial transcriptomics
vascularization
white adipose tissue

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Cite this

Nigro, P., Vamvini, M., Yang, J., Caputo, T., Ho, L. L., Carbone, N. P., Papadopoulos, D., Conlin, R., He, J., Hirshman, M. F., White, J. D., Robidoux, J., Hickner, R. C., Nielsen, S., Pedersen, B. K., Kellis, M., Middelbeek, R. J. W., & Goodyear, L. J. (2023). Exercise training remodels inguinal white adipose tissue through adaptations in innervation, vascularization, and the extracellular matrix. Cell Reports, 42(4), [112392]. https://doi.org/10.1016/j.celrep.2023.112392

Exercise training remodels inguinal white adipose tissue through adaptations in innervation, vascularization, and the extracellular matrix. / Nigro, Pasquale; Vamvini, Maria; Yang, Jiekun; Caputo, Tiziana; Ho, Li Lun; Carbone, Nicholas P.; Papadopoulos, Danae; Conlin, Royce; He, Jie; Hirshman, Michael F.; White, Joseph D.; Robidoux, Jacques; Hickner, Robert C.; Nielsen, Søren; Pedersen, Bente K.; Kellis, Manolis; Middelbeek, Roeland J.W.; Goodyear, Laurie J.

In: Cell Reports, Vol. 42, No. 4, 112392, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Nigro, P, Vamvini, M, Yang, J, Caputo, T, Ho, LL, Carbone, NP, Papadopoulos, D, Conlin, R, He, J, Hirshman, MF, White, JD, Robidoux, J, Hickner, RC, Nielsen, S, Pedersen, BK, Kellis, M, Middelbeek, RJW & Goodyear, LJ 2023, 'Exercise training remodels inguinal white adipose tissue through adaptations in innervation, vascularization, and the extracellular matrix', Cell Reports, vol. 42, no. 4, 112392. https://doi.org/10.1016/j.celrep.2023.112392

Nigro, Pasquale ; Vamvini, Maria ; Yang, Jiekun ; Caputo, Tiziana ; Ho, Li Lun ; Carbone, Nicholas P. ; Papadopoulos, Danae ; Conlin, Royce ; He, Jie ; Hirshman, Michael F. ; White, Joseph D. ; Robidoux, Jacques ; Hickner, Robert C. ; Nielsen, Søren ; Pedersen, Bente K. ; Kellis, Manolis ; Middelbeek, Roeland J.W. ; Goodyear, Laurie J. / Exercise training remodels inguinal white adipose tissue through adaptations in innervation, vascularization, and the extracellular matrix. In: Cell Reports. 2023 ; Vol. 42, No. 4.

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AU - Carbone, Nicholas P.

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AU - Hickner, Robert C.

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AB - Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood, and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses, we find that 11 days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition and increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism.

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