Acetyl-CoA-Carboxylase 1-mediated de novo fatty acid synthesis sustains Lgr5+ intestinal stem cell function

Shuting Li, Chia-Wen Lu, Elia C. Diem, Wang Li, Melanie Guderian, Marc Lindenberg, Friederike Kruse, Manuela Buettner, Stefan Floess, Markus R. Winny, Robert Geffers, Hans-Hermann Richnow, Wolf-Rainer Abraham, Guntram A. Grassl and Matthias Lochner ()
Additional contact information
Shuting Li: Hannover Medical School
Chia-Wen Lu: Hannover Medical School
Elia C. Diem: Hannover Medical School
Wang Li: Helmholtz Centre for Environmental Research – UFZ
Melanie Guderian: Hannover Medical School
Marc Lindenberg: Hannover Medical School
Friederike Kruse: Helmholtz Centre for Infection Research
Manuela Buettner: Hannover Medical School
Stefan Floess: Helmholtz Centre for Infection Research
Markus R. Winny: Visceral and Transplant Surgery, Hannover Medical School
Robert Geffers: Helmholtz Centre for Infection Research
Hans-Hermann Richnow: Helmholtz Centre for Environmental Research – UFZ
Wolf-Rainer Abraham: Helmholtz Centre for Infection Research
Guntram A. Grassl: Hannover Medical School
Matthias Lochner: Hannover Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Basic processes of the fatty acid metabolism have an important impact on the function of intestinal epithelial cells (IEC). However, while the role of cellular fatty acid oxidation is well appreciated, it is not clear how de novo fatty acid synthesis (FAS) influences the biology of IECs. We report here that interfering with de novo FAS by deletion of the enzyme Acetyl-CoA-Carboxylase (ACC)1 in IECs results in the loss of epithelial crypt structures and a specific decline in Lgr5+ intestinal epithelial stem cells (ISC). Mechanistically, ACC1-mediated de novo FAS supports the formation of intestinal organoids and the differentiation of complex crypt structures by sustaining the nuclear accumulation of PPARδ/β-catenin in ISCs. The dependency of ISCs on cellular de novo FAS is tuned by the availability of environmental lipids, as an excess delivery of external fatty acids is sufficient to rescue the defect in crypt formation. Finally, inhibition of ACC1 reduces the formation of tumors in colitis-associated colon cancer, together highlighting the importance of cellular lipogenesis for sustaining ISC function and providing a potential perspective to colon cancer therapy.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-31725-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31725-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-31725-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().