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Decreased intestinal nutrient response in diet-induced obese rats: role of gut peptides and nutrient receptors

International Journal of Obesity volume 37, pages 375–381 (2013)Cite this article

Subjects

Abstract

Background and Aims:

Diet-induced obesity (DIO) is an excellent model for examining human obesity comprising both genotypic and environmental (diet) factors. Decreased responsiveness to peripheral satiety signaling may be responsible for the hyperphagia in this model. In this study, we investigated responses to nutrient-induced satiation in outbred DIO and DIO-resistant (DR) rats fed a high-energy/high-fat (HE/HF) diet as well as intestinal satiety peptide content, intestinal nutrient-responsive receptor abundance and vagal anorectic receptor expression.

Methods:

Outbred DIO and DR rats fed a HE/HF diet were tested for short-term feeding responses following nutrient (glucose and intralipid (IL)) gastric loads. Gene and protein expressions of intestinal satiety peptides and fatty acid-responsive receptors were examined from isolated proximal intestinal epithelial cells and cholecystokinin-1 receptor (CCK-1R) and leptin receptor (LepR) mRNA from the nodose ganglia of DIO and DR animals.

Results:

DIO rats were less responsive to IL- (P<0.05) but not glucose-induced suppression of food intake compared with DR rats. DIO rats exhibited decreased CCK, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1; P<0.05 for each) protein expression compared with DR rats. Also, DIO rats expressed more G-protein-coupled receptor 40 (GPR40; P<0.0001), GPR41 (P<0.001) and GPR120 (P<0.01) relative to DR rats. Finally, there were no differences in mRNA expression for CCK-1R and LepR in the nodose ganglia of DIO and DR rats.

Conclusions:

Development of DIO may be partly due to decreased fat-induced satiation through low levels of endogenous satiety peptides, and changes in intestinal nutrient receptors.

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Acknowledgements

We thank Muriel Thomas, Marie-Louise Noordine and Leila Ben Yahia for their assistance with the collection of intestinal epithelial cells and Tomas de Wouters for his assistance with qRT-PCR experiments.

Authors Contributions

FAD, TDS and MC were responsible for study concept and design. FAD, TDSYS and MC were responsible for acquisition of data. FAD and TDS were responsible for statistical analysis. FAD, TDS and MC were responsible for interpretation of the data, drafting of the manuscript and critical revisions for important intellectual content.

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Authors and Affiliations

  1. INRA, Centre de Recherche de Jouy-en-Josas, UMR 1319, MICALIS, Neurobiology of Ingestive Behavior, Domaine de Vilvert, Jouy-en-Josas, France

    F A Duca, T D Swartz, Y Sakar & M Covasa

  2. Pierre and Marie Curie University, Paris, France

    F A Duca & T D Swartz

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

    M Covasa

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  1. F A Duca
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Correspondence to M Covasa.

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Duca, F., Swartz, T., Sakar, Y. et al. Decreased intestinal nutrient response in diet-induced obese rats: role of gut peptides and nutrient receptors. Int J Obes 37, 375–381 (2013). https://doi.org/10.1038/ijo.2012.45

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