Dietary omega-6 lipids promote post-injury aberrant bone formation in obesity
Stefanie L. Moye, Monisha Mittal, Tarun Srinivasan, Sneha Korlakunta, Chase A. Pagani, Ayelet Dar, Oromo Geshow, Dylan Feist, Lauren G. Zacharias, Zhao Li, Aaron W. James, Gerta Hoxhaj, Andrew M. Smith, Katherine A. Gallagher, Thomas P. Mathews, Robert J. Tower, Benjamin Levi
Stefanie L. Moye, Monisha Mittal, Tarun Srinivasan, Sneha Korlakunta, Chase A. Pagani, Ayelet Dar, Oromo Geshow, Dylan Feist, Lauren G. Zacharias, Zhao Li, Aaron W. James, Gerta Hoxhaj, Andrew M. Smith, Katherine A. Gallagher, Thomas P. Mathews, Robert J. Tower, Benjamin Levi
View: Text | PDF
Research In-Press Preview Bone biology Inflammation Metabolism

Dietary omega-6 lipids promote post-injury aberrant bone formation in obesity

Abstract

Obesity is associated with impaired wound healing, but the mechanisms linking excess adiposity to aberrant tissue repair remain unresolved. Heterotopic ossification (HO) is a severe example of pathologic tissue repair in which mesenchymal progenitor cells (MPCs) undergo aberrant osteochondral differentiation within soft tissue, leading to joint contractures and pain. Here, we show that accumulation of dietary omega-6 (ω-6) lipids in the injury site is a key mechanism linking obesity to HO. Specifically, in mice fed a high-fat diet (HFD), injured tissues were enriched in linoleic and arachidonic acids, providing substrate for myeloid cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) production. PGE2 then drove a transcriptional program in mesenchymal progenitor cells that promoted osteochondral differentiation. An isocaloric, low linoleic acid HFD reduced HO despite comparable obesity, demonstrating that dietary lipid composition, rather than adiposity alone, drove pathological repair. Clinical data mirrored these findings, showing that obesity conferred increased HO risk, and COX-2 inhibition reduced HO exclusively in obese patients. Together, these findings identify injury site ω-6 lipid enrichment as the key signal linking the diet to MPC reprogramming, pointing to dietary lipid modulation as an actionable strategy to limit HO in obesity.

Authors

Stefanie L. Moye, Monisha Mittal, Tarun Srinivasan, Sneha Korlakunta, Chase A. Pagani, Ayelet Dar, Oromo Geshow, Dylan Feist, Lauren G. Zacharias, Zhao Li, Aaron W. James, Gerta Hoxhaj, Andrew M. Smith, Katherine A. Gallagher, Thomas P. Mathews, Robert J. Tower, Benjamin Levi

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

- Download (4.62 MB)

Advertisement