Universität zu Köln

Vonolfen, Maximilian C. ORCID: 0009-0007-8706-4099, Meyer zu Altenschildesche, Fenja L., Nam, Hyuck-Jin, Brodesser, Susanne ORCID: 0000-0001-5631-0663, Gyenis, Akos ORCID: 0000-0002-8104-7681, Buellesbach, Jan, Lam, Geanette, Thummel, Carl S. and Storelli, Gilles ORCID: 0000-0002-3558-390X (2024). Drosophila HNF4 acts in distinct tissues to direct a switch between lipid storage and export in the gut. Cell Reports, 43 (9). pp. 1-26. Elsevier. ISSN 2211-1247

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Abstract

[Artikel-Nr.: 114693] Nutrient digestion, absorption, and export must be coordinated in the gut to meet the nutritional needs of the organism. We used the Drosophila intestine to characterize the mechanisms that coordinate the fate of dietary lipids. We identified enterocytes specialized in absorbing and exporting lipids to peripheral organs. Distinct hepatocyte-like cells, called oenocytes, communicate with these enterocytes to adjust intestinal lipid storage and export. A single transcription factor, Drosophila hepatocyte nuclear factor 4 (dHNF4), supports this gut-liver axis. In enterocytes, dHNF4 maximizes dietary lipid export by preventing their sequestration in cytoplasmic lipid droplets. In oenocytes, dHNF4 promotes the expression of the insulin antagonist ImpL2 to activate Foxo and suppress lipid retention in enterocytes. Disruption of this switch between lipid storage and export is associated with intestinal inflammation, suggesting a lipidic origin for inflammatory bowel diseases. These studies establish dHNF4 as a central regulator of intestinal metabolism and inter-organ lipid trafficking.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Vonolfen, Maximilian C. UNSPECIFIED https://orcid.org/0009-0007-8706-4099 UNSPECIFIED Meyer zu Altenschildesche, Fenja L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nam, Hyuck-Jin UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodesser, Susanne UNSPECIFIED https://orcid.org/0000-0001-5631-0663 UNSPECIFIED Gyenis, Akos UNSPECIFIED https://orcid.org/0000-0002-8104-7681 UNSPECIFIED Buellesbach, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Lam, Geanette UNSPECIFIED UNSPECIFIED UNSPECIFIED Thummel, Carl S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Storelli, Gilles UNSPECIFIED https://orcid.org/0000-0002-3558-390X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-813805
Identification Number:	10.1016/j.celrep.2024.114693
Journal or Publication Title:	Cell Reports
Volume:	43
Number:	9
Page Range:	pp. 1-26
Number of Pages:	26
Date:	September 2024
Publisher:	Elsevier
ISSN:	2211-1247
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	Life sciences Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language hepatocyte nuclear factor 4 ; enterocyte ; oenocyte ; lipoprotein ; chylomicron ; inflammation ; gut-liver axis ; lipid ; metabolism ; Drosophila English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81380