Exercise Training Remodels Adipocyte-Specific Extracellular Matrix Proteins and Alters Innervation and Vascularization in Inguinal White Adipose Tissue (iWAT)

Nigro, P.; Vamvini, M.; Yang, J. J.; Caputo, T.; Ho, L.-L.; Papadopoulos, D.; Carbone, N. P.; Colin, R.; He, J.; Michael, H. F.; White, J. D.; Robidoux, J.; Hickner, R.; Nielsen, S.; Pedersen, B. K.; Kellis, M.; Middelbeek, R.; Goodyear, L. J.

doi:10.1101/2022.08.09.503375

bioRxiv · 10.1101/2022.08.09.503375

Exercise Training Remodels Adipocyte-Specific Extracellular Matrix Proteins and Alters Innervation and Vascularization in Inguinal White Adipose Tissue (iWAT)

Nigro, P.·Vamvini, M.·Yang, J. J.·Caputo, T.·Ho, L.-L.·Papadopoulos, D.·Carbone, N. P.·Colin, R.·He, J.·Michael, H. F.·White, J. D.·Robidoux, J.·Hickner, R.·Nielsen, S.·Pedersen, B. K.·Kellis, M.·Middelbeek, R.·Goodyear, L. J.

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Abstract

Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. Extracellular matrix (ECM) composition, innervation, and vascularization are all important regulators of iWAT function, yet whether exercise training improves these structural components of iWAT is unknown. Using biochemical, imaging, and multi-omics analyses we find that 11-days of wheel running in male mice causes profound iWAT remodeling including decreased ECM deposition and increased vascularization and innervation. We identify adipose stem cells as the main contributors to training-induced ECM remodeling, determine that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations, 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. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/503375v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@fd590eorg.highwire.dtl.DTLVardef@e1dd02org.highwire.dtl.DTLVardef@74be24org.highwire.dtl.DTLVardef@6f6e58_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Nigro, P., Vamvini, M., Yang, J. J., Caputo, T., Ho, L.-L., Papadopoulos, D., Carbone, N. P., Colin, R., He, J., Michael, H. F., White, J. D., Robidoux, J., Hickner, R., Nielsen, S., Pedersen, B. K., Kellis, M., Middelbeek, R., Goodyear, L. J.. 2022-08-11. Exercise Training Remodels Adipocyte-Specific Extracellular Matrix Proteins and Alters Innervation and Vascularization in Inguinal White Adipose Tissue (iWAT). https://doi.org/10.1101/2022.08.09.503375

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