Y Sakar1, F A Duca1, B Langelier1, F Devime1, H Blottiere1, C Delorme1, P Renault1, M Covasa2. 1. 1] UMR1913-MICALIS, INRA Centre de Recherche de Jouy-en-Josas, Jouy-en-Josas, France [2] UMR1913-MICALIS, AgroParisTech, Jouy-en-Josas, France. 2. 1] UMR1913-MICALIS, INRA Centre de Recherche de Jouy-en-Josas, Jouy-en-Josas, France [2] UMR1913-MICALIS, AgroParisTech, Jouy-en-Josas, France [3] Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA, USA [4] Department of Human Health and Development, University of Suceava, Suceava, Romania.
Abstract
BACKGROUND AND OBJECTIVES: Gut hormones secreted by enteroendocrine cells (EECs) play a major role in energy regulation. Differentiation of EEC is controlled by the expression of basic helix-loop-helix (bHLH) transcription factors. High-fat (HF) feeding alters gut hormone levels; however, the impact of HF feeding on bHLH transcription factors in mediating EEC differentiation and subsequent gut hormone secretion and expression is not known. METHODS: Outbred Sprague-Dawley rats were maintained on chow or HF diet for 12 weeks. Gene and protein expression of intestinal bHLH transcription factors, combined with immunofluorescence studies, were analyzed for both groups in the small intestine and colon. Gut permeability, intestinal lipid and carbohydrate transporters as well as circulating levels and intestinal protein expression of gut peptides were determined. RESULTS: We showed that HF feeding resulted in hyperphagia and increased adiposity. HF-fed animals exhibited decreased expression of bHLH transcription factors controlling EEC differentiation (MATH1, NGN3, NEUROD1) and increased expression of bHLH factors modulating enterocyte expression. Furthermore, HF-fed animals had decreased number of total EECs and L-cells. This was accompanied by increased gut permeability and expression of lipid and carbohydrate transporters, and a decrease in circulating and intestinal gut hormone levels. CONCLUSIONS: Taken together, our results demonstrate that HF feeding caused decreased secretory lineage (that is, EECs) differentiation through downregulation of bHLH transcription factors, resulting in reduced EEC number and gut hormone levels. Thus, impaired EEC differentiation pathways by HF feeding may promote hyperphagia and subsequent obesity.
BACKGROUND AND OBJECTIVES: Gut hormones secreted by enteroendocrine cells (EECs) play a major role in energy regulation. Differentiation of EEC is controlled by the expression of basic helix-loop-helix (bHLH) transcription factors. High-fat (HF) feeding alters gut hormone levels; however, the impact of HF feeding on bHLH transcription factors in mediating EEC differentiation and subsequent gut hormone secretion and expression is not known. METHODS: Outbred Sprague-Dawley rats were maintained on chow or HF diet for 12 weeks. Gene and protein expression of intestinal bHLH transcription factors, combined with immunofluorescence studies, were analyzed for both groups in the small intestine and colon. Gut permeability, intestinal lipid and carbohydrate transporters as well as circulating levels and intestinal protein expression of gut peptides were determined. RESULTS: We showed that HF feeding resulted in hyperphagia and increased adiposity. HF-fed animals exhibited decreased expression of bHLH transcription factors controlling EEC differentiation (MATH1, NGN3, NEUROD1) and increased expression of bHLH factors modulating enterocyte expression. Furthermore, HF-fed animals had decreased number of total EECs and L-cells. This was accompanied by increased gut permeability and expression of lipid and carbohydrate transporters, and a decrease in circulating and intestinal gut hormone levels. CONCLUSIONS: Taken together, our results demonstrate that HF feeding caused decreased secretory lineage (that is, EECs) differentiation through downregulation of bHLH transcription factors, resulting in reduced EEC number and gut hormone levels. Thus, impaired EEC differentiation pathways by HF feeding may promote hyperphagia and subsequent obesity.
Authors: Shay Porat; Noa Weinberg-Corem; Sharona Tornovsky-Babaey; Rachel Schyr-Ben-Haroush; Ayat Hija; Miri Stolovich-Rain; Daniela Dadon; Zvi Granot; Vered Ben-Hur; Peter White; Christophe A Girard; Rotem Karni; Klaus H Kaestner; Frances M Ashcroft; Mark A Magnuson; Ann Saada; Joseph Grimsby; Benjamin Glaser; Yuval Dor Journal: Cell Metab Date: 2011-04-06 Impact factor: 27.287
Authors: Josselin Soyer; Lydie Flasse; Wolfgang Raffelsberger; Anthony Beucher; Christophe Orvain; Bernard Peers; Philippe Ravassard; Julien Vermot; Marianne L Voz; Georg Mellitzer; Gérard Gradwohl Journal: Development Date: 2010-01 Impact factor: 6.868
Authors: Kirsten Vollmer; Jens J Holst; Birgit Baller; Mark Ellrichmann; Michael A Nauck; Wolfgang E Schmidt; Juris J Meier Journal: Diabetes Date: 2007-12-05 Impact factor: 9.461
Authors: Sarah F Andres; M Agostina Santoro; Amanda T Mah; J Adeola Keku; Amy E Bortvedt; R Eric Blue; P Kay Lund Journal: Am J Physiol Gastrointest Liver Physiol Date: 2014-11-13 Impact factor: 4.052
Authors: Alicia L Carreiro; Jaapna Dhillon; Susannah Gordon; Kelly A Higgins; Ashley G Jacobs; Breanna M McArthur; Benjamin W Redan; Rebecca L Rivera; Leigh R Schmidt; Richard D Mattes Journal: Annu Rev Nutr Date: 2016-07-17 Impact factor: 11.848
Authors: Amanda T Mah; Laurianne Van Landeghem; Hannah E Gavin; Scott T Magness; P Kay Lund Journal: Endocrinology Date: 2014-06-10 Impact factor: 4.736
Authors: Paul Richards; Ramona Pais; Abdella M Habib; Cheryl A Brighton; Giles S H Yeo; Frank Reimann; Fiona M Gribble Journal: Peptides Date: 2015-07-03 Impact factor: 3.750