Journal article
Adipocyte autophagy limits gut inflammation by controlling oxylipin and IL-10
- Abstract:
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Lipids play a major role in inflammatory diseases by altering inflammatory cell functions, either through their function as energy substrates or as lipid mediators such as oxylipins. Autophagy, a lysosomal degradation pathway that limits inflammation, is known to impact on lipid availability, however, whether this controls inflammation remains unexplored. We found that upon intestinal inflammation visceral adipocytes upregulate autophagy and that adipocyte-specific loss of the autophagy gene Atg7 exacerbates inflammation. While autophagy decreased lipolytic release of free fatty acids, loss of the major lipolytic enzyme Pnpla2/Atgl in adipocytes did not alter intestinal inflammation, ruling out free fatty acids as anti-inflammatory energy substrates. Instead, Atg7-deficient adipose tissues exhibited an oxylipin imbalance, driven through an NRF2-mediated upregulation of Ephx1. This shift reduced secretion of IL-10 from adipose tissues, which was dependent on the cytochrome P450-EPHX pathway, and lowered circulating levels of IL-10 to exacerbate intestinal inflammation. These results suggest an underappreciated fat-gut crosstalk through an autophagy-dependent regulation of anti-inflammatory oxylipins via the cytochrome P450-EPHX pathway, indicating a protective effect of adipose tissues for distant inflammation.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 5.2MB, Terms of use)
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- Publisher copy:
- 10.15252/embj.2022112202
Authors
- Publisher:
- EMBO Press
- Journal:
- EMBO Journal More from this journal
- Volume:
- 42
- Issue:
- 6
- Article number:
- e112202
- Publication date:
- 2023-02-16
- Acceptance date:
- 2023-01-17
- DOI:
- EISSN:
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1460-2075
- ISSN:
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0261-4189
- Language:
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English
- Keywords:
- Pubs id:
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1328756
- Local pid:
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pubs:1328756
- Deposit date:
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2023-03-03
Terms of use
- Copyright holder:
- Richter et al.
- Copyright date:
- 2023
- Rights statement:
- © 2023 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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