Simon Ducheix1, Claudia Peres1, Jennifer Härdfeldt1, Carla Frau2, Gabriele Mocciaro3, Elena Piccinin1, Jean-Marc Lobaccaro4, Stefania De Santis5, Marcello Chieppa5, Justine Bertrand-Michel6, Michelina Plateroti2, Julian L Griffin3, Carlo Sabbà1, James M Ntambi7, Antonio Moschetta8. 1. Clinica Medica Cesare Frugoni, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Bari, Italia. 2. Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS UMR5286, Université de Lyon, Département de la recherche, Lyon, France. 3. Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom. 4. INSERM U 1103, CNRS, UMR 6293, Université Clermont Auvergne, GReD, F-6300 Aubière, France; Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France. 5. IRCCS National Institute of Gastroenterology S. de Bellis, Castellana Grotte, Italy. 6. Lipidomic Facility, MetaboHUB, INSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France. 7. University of Wisconsin Madison, Departments of Biochemistry and of Nutritional Sciences, Madison, Wisconsin. 8. Clinica Medica Cesare Frugoni, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Bari, Italia; IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italia. Electronic address: antonio.moschetta@uniba.it.
Abstract
BACKGROUND & AIMS: The enzyme stearoyl-coenzyme A desaturase 1 (SCD or SCD1) produces monounsaturated fatty acids by introducing double bonds into saturated bonds between carbons 9 and 10, with oleic acid as the main product. SCD1 is present in the intestinal epithelium, and fatty acids regulate cell proliferation, so we investigated the effects of SCD1-induced production of oleic acid in enterocytes in mice. METHODS: We generated mice with disruption of Scd1 selectively in the intestinal epithelium (iScd1-/- mice) on a C57BL/6 background; iScd1+/+ mice were used as controls. We also generated iScd1-/-ApcMin/+ mice and studied cancer susceptibility. Mice were fed a chow, oleic acid-deficient, or oleic acid-rich diet. Intestinal tissues were collected and analyzed by histology, reverse transcription quantitative polymerase chain reaction, immunohistochemistry, and mass spectrometry, and tumors were quantified and measured. RESULTS: Compared with control mice, the ileal mucosa of iScd1-/- mice had a lower proportion of palmitoleic (C16:1 n-7) and oleic acids (C18:1 n-9), with accumulation of stearic acid (C18:0); this resulted a reduction of the Δ9 desaturation ratio between monounsaturated (C16:1 n-7 and C18:1 n-9) and saturated (C16:0 and C18:0) fatty acids. Ileal tissues from iScd1-/- mice had increased expression of markers of inflammation activation and crypt proliferative genes compared with control mice. The iScd1-/-ApcMin/+ mice developed more and larger tumors than iScd1+/+ApcMin/+ mice. iScd1-/-ApcMin/+ mice fed the oleic acid-rich diet had reduced intestinal inflammation and significantly lower tumor burden compared with mice fed a chow diet. CONCLUSIONS: In studies of mice, we found intestinal SCD1 to be required for synthesis of oleate in the enterocytes and maintenance of fatty acid homeostasis. Dietary supplementation with oleic acid reduces intestinal inflammation and tumor development in mice.
BACKGROUND & AIMS: The enzyme stearoyl-coenzyme A desaturase 1 (SCD or SCD1) produces monounsaturated fatty acids by introducing double bonds into saturated bonds between carbons 9 and 10, with oleic acid as the main product. SCD1 is present in the intestinal epithelium, and fatty acids regulate cell proliferation, so we investigated the effects of SCD1-induced production of oleic acid in enterocytes in mice. METHODS: We generated mice with disruption of Scd1 selectively in the intestinal epithelium (iScd1-/- mice) on a C57BL/6 background; iScd1+/+ mice were used as controls. We also generated iScd1-/-ApcMin/+ mice and studied cancer susceptibility. Mice were fed a chow, oleic acid-deficient, or oleic acid-rich diet. Intestinal tissues were collected and analyzed by histology, reverse transcription quantitative polymerase chain reaction, immunohistochemistry, and mass spectrometry, and tumors were quantified and measured. RESULTS: Compared with control mice, the ileal mucosa of iScd1-/- mice had a lower proportion of palmitoleic (C16:1 n-7) and oleic acids (C18:1 n-9), with accumulation of stearic acid (C18:0); this resulted a reduction of the Δ9 desaturation ratio between monounsaturated (C16:1 n-7 and C18:1 n-9) and saturated (C16:0 and C18:0) fatty acids. Ileal tissues from iScd1-/- mice had increased expression of markers of inflammation activation and crypt proliferative genes compared with control mice. The iScd1-/-ApcMin/+ mice developed more and larger tumors than iScd1+/+ApcMin/+ mice. iScd1-/-ApcMin/+ mice fed the oleic acid-rich diet had reduced intestinal inflammation and significantly lower tumor burden compared with mice fed a chow diet. CONCLUSIONS: In studies of mice, we found intestinal SCD1 to be required for synthesis of oleate in the enterocytes and maintenance of fatty acid homeostasis. Dietary supplementation with oleic acid reduces intestinal inflammation and tumor development in mice.
Authors: Elena Piccinin; Marica Cariello; Stefania De Santis; Simon Ducheix; Carlo Sabbà; James M Ntambi; Antonio Moschetta Journal: Nutrients Date: 2019-09-24 Impact factor: 5.717
Authors: Thomas Lundåsen; Matteo Pedrelli; Bodil Bjørndal; Björn Rozell; Raoul V Kuiper; Lena Burri; Chiara Pavanello; Marta Turri; Jon Skorve; Rolf K Berge; Stefan E H Alexson; Veronika Tillander Journal: PLoS One Date: 2020-03-16 Impact factor: 3.240