High-fat feeding drives the intestinal production and assembly of C <sub>16:0</sub> ceramides in chylomicrons
Consumption of a diet rich in saturated fat increases lipid absorption from the intestine, assembly into chylomicrons, and delivery to metabolic tissues via the lymphatic and circulatory systems. Accumulation of ceramide lipids, composed of sphingosine and a fatty acid, in metabolic tissues contributes to the pathogenesis of cardiovascular diseases, type 2 diabetes mellitus and cancer. Using a mesenteric lymph duct cannulated rat model, we showed that ceramides are generated by the intestine and assembled into chylomicrons, which are transported via the mesenteric lymphatic system. A lipidomic screen of intestinal-derived chylomicrons identified a diverse range of fatty acid, sphingolipid, and glycerolipid species that have not been previously detected in chylomicrons, including the metabolically deleterious C<sub>16:0</sub> ceramide that increased in response to high-fat feeding in rats and human high-lipid meal replacement enteral feeding. In conclusion, high-fat feeding increases the export of intestinal-derived C<sub>16:0</sub> ceramide in chylomicrons, identifying a potentially unknown mechanism through which ceramides are transported systemically to contribute to metabolic dysfunction.
Authors
- Surafel Tegegne (ORCID: https://orcid.org/0000-0002-3280-9117)
- Natalie L. Trevaskis (ORCID: https://orcid.org/0000-0001-9538-549X)
- Anthony R.J. Phillips (ORCID: https://orcid.org/0000-0001-6143-5866)
- Darren J. Creek (ORCID: https://orcid.org/0000-0001-7497-7082)
- Mark A. Febbraio (ORCID: https://orcid.org/0000-0002-9296-4418)
- John A. Windsor (ORCID: https://orcid.org/0000-0001-5995-5432)
- Colby Zaph (ORCID: https://orcid.org/0000-0002-9889-9848)
- Alistair B.J. Escott
- Jiwon Hong (ORCID: https://orcid.org/0000-0003-0936-3281)
- Michael Mah (ORCID: https://orcid.org/0009-0001-1297-0341)
- Susanne Brodesser (ORCID: https://orcid.org/0000-0001-5631-0663)
- Enyuan Cao (ORCID: https://orcid.org/0000-0002-9689-4517)
- Sarah M. Turpin-Nolan (ORCID: https://orcid.org/0000-0002-7469-7934)
- Gracia Gracia (ORCID: https://orcid.org/0009-0000-8552-2323)
- Dovile Anderson (ORCID: https://orcid.org/0000-0003-0284-471X)
- Joel Schmitz
Institutions
- University of Auckland (NZ)
- Australian Regenerative Medicine Institute (AU)
- Auckland City Hospital (NZ)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Monash University (AU)
Publication Details
- Journal
- Science Advances
- Published
- 2024-08-23
- DOI
- https://doi.org/10.1126/sciadv.adp2254
- Citations
- 10
- Primary Topic
- Sphingolipid Metabolism and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 2.34
Funders
- Monash University