Internet publication
Cell-extrinsic autophagy in mature adipocytes regulates anti-inflammatory response to intestinal tissue injury through lipid mobilization
- Abstract:
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Autophagy is a critical cellular recycling pathway which is genetically linked to the development of intestinal inflammation in humans. Inflammation drives adipose tissue breakdown and provision of major nutrients such as free fatty acids (FFA). However, the effect of autophagy-mediated FFA release by adipocytes in immune-mediated inflammatory diseases remains unexplored.
In a mouse model of intestinal inflammation, we found that visceral adipocytes upregulate autophagy at peak inflammation. Adipocyte-specific loss of the key autophagy gene Atg7 (Atg7Ad) resulted in the exacerbation of intestinal inflammation. TNFα-induced lipolysis was impaired in Atg7-deficient adipocytes leading to the reduced availability of several FFA species, and decreased expression of the FFA transporter CD36 on adipose tissue macrophages (ATMs). Visceral adipose tissues from Atg7Ad mice released less IL-10 resulting in lower levels of circulating IL-10 in colitis. ATMs present the main source of adipose tissue-derived IL-10 during colitis. In vitro assays confirmed that FFA restriction from macrophages reduced CD36 expression and diminished IL-10 production.
Taken together, our study demonstrates that autophagy-mediated FFA release from adipocytes directs anti-inflammatory responses in ATMs, which in turn conveys protective effects for distant intestinal inflammation.
- Publication status:
- Published
- Peer review status:
- Not peer reviewed
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- Files:
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(Preview, Pre-print, 2.0MB, Terms of use)
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- Publisher copy:
- 10.1101/2021.10.25.465200
Authors
- Publisher:
- Cold Spring Harbor Laboratory
- Host title:
- Cold Spring Harbor Laboratory
- Publication date:
- 2021-10-26
- DOI:
- Language:
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English
- Keywords:
- Pubs id:
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1207471
- Local pid:
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pubs:1207471
- Deposit date:
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2021-11-05
Terms of use
- Copyright holder:
- Richter et al.
- Copyright date:
- 2021
- Rights statement:
- The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
- Licence:
- CC Attribution (CC BY)
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