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Impact of high-fat feeding on basic helix–loop–helix transcription factors controlling enteroendocrine cell differentiation

International Journal of Obesity volume 38, pages 1440–1448 (2014)Cite this article

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A Retraction to this article was published on 06 July 2016

A Corrigendum to this article was published on 11 November 2014

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.

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Acknowledgements

We thank the ANAXEM team for their assistance in the animal facilities, and Julie Cadiou for assisting with the behavioral experiments. This study was supported by INRA through a scientific package to MC and by the Romanian National Program PN-II-ID-PCE-2012-4-0608 no. 48/02.09.2013, ‘Analysis of novel risk factors influencing control of food intake and regulation of body weight’.

AUTHOR CONTRIBUTIONS

YS, MC, HB and CD designed the study. YS, MC, FD and BL researched the data. YS, FAD and MC wrote and revised the manuscript.

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Authors and Affiliations

  1. UMR1913-MICALIS, INRA Centre de Recherche de Jouy-en-Josas, Jouy-en-Josas, France

    Y Sakar, F A Duca, B Langelier, F Devime, H Blottiere, C Delorme, P Renault & M Covasa

  2. UMR1913-MICALIS, AgroParisTech, Jouy-en-Josas, France

    Y Sakar, F A Duca, B Langelier, F Devime, H Blottiere, C Delorme, P Renault & M Covasa

  3. Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA, USA

    M Covasa

  4. Department of Human Health and Development, University of Suceava, Suceava, Romania

    M Covasa

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Correspondence to M Covasa.

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Sakar, Y., Duca, F., Langelier, B. et al. Impact of high-fat feeding on basic helix–loop–helix transcription factors controlling enteroendocrine cell differentiation. Int J Obes 38, 1440–1448 (2014). https://doi.org/10.1038/ijo.2014.20

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