Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism

Patrick O'Brien; Ge Han; Priya Ganpathy; Shweta Pitre; Yi Zhang; John Ryan; Pei Ying Sim; Scott V Harding; Robert Gray; Victor R Preedy; Thomas A B Sanders; Christopher P Corpe

doi:10.3390/ijms22010137

Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism

Patrick O'Brien, Ge Han, Priya Ganpathy, Shweta Pitre, Yi Zhang, John Ryan, Pei Ying Sim, Scott V Harding, Robert Gray, Victor R Preedy, Thomas A B Sanders, Christopher P Corpe

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Abstract

The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male mice chronically fed a control diet or a high sucrose diet (HSD) and analysed for changes in gene, protein and metabolite levels. In HSD mice, GIT expression levels of fat oxidation genes were reduced, and increased de novo lipogenesis was evident in ileum. Gene expression levels of the putative sugar sensor, slc5a4a and slc5a4b, and fat sensor, cd36, were downregulated in the small intestines of HSD mice. In HSD mice, there was also evidence of bacterial overgrowth and a lipopolysaccharide activated inflammatory pathway involving inducible nitric oxide synthase (iNOS). In Caco-2 cells, sucrose significantly increased the expression levels of the nos2, iNOS and nitric oxide (NO) gas levels. In conclusion, sucrose fed induced obesity/diabetes is associated with changes in GI macronutrient sensing, appetite regulation and nutrient metabolism and intestinal microflora. These may be important drivers, and thus therapeutic targets, of diet-related metabolic disease.

Original language	English
Article number	137
Pages (from-to)	1-26
Number of pages	26
Journal	International Journal of Molecular Sciences
Volume	22
Issue number	1
Early online date	25 Dec 2020
DOIs	https://doi.org/10.3390/ijms22010137
Publication status	Published - 1 Jan 2021

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Chronic Effects of a_O'BRIEN_Acc16Dec2020Epub25Dec2020_GOLD VoR(CC BY)Final published version, 4.24 MBLicence: CC BY

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O'Brien, P., Han, G., Ganpathy, P., Pitre, S., Zhang, Y., Ryan, J., Sim, P. Y., Harding, S. V., Gray, R., Preedy, V. R., Sanders, T. A. B., & Corpe, C. P. (2021). Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism. International Journal of Molecular Sciences, 22(1), 1-26. Article 137. https://doi.org/10.3390/ijms22010137

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title = "Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism",

abstract = "The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male mice chronically fed a control diet or a high sucrose diet (HSD) and analysed for changes in gene, protein and metabolite levels. In HSD mice, GIT expression levels of fat oxidation genes were reduced, and increased de novo lipogenesis was evident in ileum. Gene expression levels of the putative sugar sensor, slc5a4a and slc5a4b, and fat sensor, cd36, were downregulated in the small intestines of HSD mice. In HSD mice, there was also evidence of bacterial overgrowth and a lipopolysaccharide activated inflammatory pathway involving inducible nitric oxide synthase (iNOS). In Caco-2 cells, sucrose significantly increased the expression levels of the nos2, iNOS and nitric oxide (NO) gas levels. In conclusion, sucrose fed induced obesity/diabetes is associated with changes in GI macronutrient sensing, appetite regulation and nutrient metabolism and intestinal microflora. These may be important drivers, and thus therapeutic targets, of diet-related metabolic disease.",

author = "Patrick O'Brien and Ge Han and Priya Ganpathy and Shweta Pitre and Yi Zhang and John Ryan and Sim, {Pei Ying} and Harding, {Scott V} and Robert Gray and Preedy, {Victor R} and Sanders, {Thomas A B} and Corpe, {Christopher P}",

note = "Funding Information: Acknowledgments: This work was supported by the King{\textquoteright}s College London studentship fund (P.O.). We are also grateful for the assistance of Arianna Psichas, Matt Arno and Estibaliz Aldecoa-Otalora for their gene micro array work. Publisher Copyright: {\textcopyright} 2020 by the authors. Li-censee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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O'Brien, P , Han, G, Ganpathy, P, Pitre, S, Zhang, Y, Ryan, J, Sim, PY, Harding, SV, Gray, R , Preedy, VR , Sanders, TAB & Corpe, CP 2021, 'Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism', International Journal of Molecular Sciences, vol. 22, no. 1, 137, pp. 1-26. https://doi.org/10.3390/ijms22010137

TY - JOUR

T1 - Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism

AU - O'Brien, Patrick

AU - Han, Ge

AU - Ganpathy, Priya

AU - Pitre, Shweta

AU - Zhang, Yi

AU - Ryan, John

AU - Sim, Pei Ying

AU - Harding, Scott V

AU - Gray, Robert

AU - Preedy, Victor R

AU - Sanders, Thomas A B

AU - Corpe, Christopher P

N1 - Funding Information: Acknowledgments: This work was supported by the King’s College London studentship fund (P.O.). We are also grateful for the assistance of Arianna Psichas, Matt Arno and Estibaliz Aldecoa-Otalora for their gene micro array work. Publisher Copyright: © 2020 by the authors. Li-censee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male mice chronically fed a control diet or a high sucrose diet (HSD) and analysed for changes in gene, protein and metabolite levels. In HSD mice, GIT expression levels of fat oxidation genes were reduced, and increased de novo lipogenesis was evident in ileum. Gene expression levels of the putative sugar sensor, slc5a4a and slc5a4b, and fat sensor, cd36, were downregulated in the small intestines of HSD mice. In HSD mice, there was also evidence of bacterial overgrowth and a lipopolysaccharide activated inflammatory pathway involving inducible nitric oxide synthase (iNOS). In Caco-2 cells, sucrose significantly increased the expression levels of the nos2, iNOS and nitric oxide (NO) gas levels. In conclusion, sucrose fed induced obesity/diabetes is associated with changes in GI macronutrient sensing, appetite regulation and nutrient metabolism and intestinal microflora. These may be important drivers, and thus therapeutic targets, of diet-related metabolic disease.

AB - The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male mice chronically fed a control diet or a high sucrose diet (HSD) and analysed for changes in gene, protein and metabolite levels. In HSD mice, GIT expression levels of fat oxidation genes were reduced, and increased de novo lipogenesis was evident in ileum. Gene expression levels of the putative sugar sensor, slc5a4a and slc5a4b, and fat sensor, cd36, were downregulated in the small intestines of HSD mice. In HSD mice, there was also evidence of bacterial overgrowth and a lipopolysaccharide activated inflammatory pathway involving inducible nitric oxide synthase (iNOS). In Caco-2 cells, sucrose significantly increased the expression levels of the nos2, iNOS and nitric oxide (NO) gas levels. In conclusion, sucrose fed induced obesity/diabetes is associated with changes in GI macronutrient sensing, appetite regulation and nutrient metabolism and intestinal microflora. These may be important drivers, and thus therapeutic targets, of diet-related metabolic disease.

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U2 - 10.3390/ijms22010137

DO - 10.3390/ijms22010137

M3 - Article

C2 - 33375525

SN - 1661-6596

VL - 22

SP - 1

EP - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

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ER -

Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism

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