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Nutritive/non-nutritive sweeteners and high fat diet contribute to dysregulation of sweet taste receptors and metabolic derangements in oral, intestinal and central nervous tissues

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Abstract

Objectives

Overconsumption of non-nutritive sweeteners is associated with obesity, whereas the underlying mechanisms remain controversial. This study aimed to investigate the effects of long-term consumption of nutritive or non-nutritive sweeteners with or without high fat diet on sweet taste receptor expression in nutrient-sensing tissues and energy regulation dependent on sweet-sensing.

Methods

50 Male Sprague–Dawley rats (140–160 g) were assigned to 10 groups (n = 5/group). All received fructose at 2.5% or 10%, sucralose at 0.01% or 0.015% or water with a normal chow diet or high fat diet for 12 weeks. Food and drink intake were monitored daily. Oral glucose tolerance test and intraperitoneal glucose tolerance test were performed at week 10 and 11 respectively. Serum was obtained for measurement of biochemical parameters. Tongue, duodenum, jejunum, ileum, colon and hypothalamus were rapidly removed to assess gene expression.

Results

Long-term consumption of sweeteners impaired glucose tolerance, increased calorie intake and body weight. A significant upregulation of sweet taste receptor expression was observed in all the four intestinal segments in groups fed 0.01% sucralose or 0.015% sucralose, most strikingly in the ileum, accompanied by elevated serum glucagon-like peptide-1 levels and up-regulated expression of sodium-dependent glucose cotransporter 1 and glucose transporter 2. A significant down-regulation in the tongue and hypothalamus was observed in groups fed 10% fructose or 0.015% sucralose, with alterations in hypothalamic appetite signals. The presence of high fat diet differentially modulates sweet taste perception in nutrient-sensing tissues.

Conclusions

Long-term consumption of whether nutritive sweeteners or non-nutritive sweeteners combined with high fat diet contribute to dysregulation of sweet taste receptor expression in oral, intestinal and central nervous tissues.

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Data availability

The datasets used and analysed in this current study are available from the corresponding author upon reasonable request.

Abbreviations

AGRP:

Agouti-related peptide

AUC:

Area under the curve

GLP-1:

Glucagon-like peptide-1

GLUT2:

Glucose transporter 2

HFD:

High-fat diet

IPGTT:

Intraperitoneal glucose tolerance test

NCD:

Normal control diet

NNS:

Non-nutritive sweetener

NPY:

Neuropeptide Y

OGTT:

Oral glucose tolerance test

SGLT-1:

Sodium-dependent glucose cotransporter 1

STR:

Sweet taste receptor

T1R2:

Taste receptor type 1 member 2

T1R3:

Taste receptor type 1 member 3

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Authors and Affiliations

  1. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University, Wuhan, 430000, China

    Yiyuan Zhang, Lu Chen, Jiefang Gao, Yahong Cheng, Fei Luo, Xinying Bai & Hong Ding

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  1. Yiyuan Zhang
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  2. Lu Chen
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Contributions

The authors’ responsibilities were as followed. YZ and HD designed research; YZ, LC, JG, YC, FL, XB conducted research; YZ and HD analyzed data; YZ wrote the paper; YZ and HD had primary responsibility for the final content. All authors read and approved the final version of the paper.

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Correspondence to Hong Ding.

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Conflict of interest

Y. Zhang, L. Chen, J. Gao, Y. Cheng, F. Luo, X. Bai, H. Ding, no conflicts of interest.

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Zhang, Y., Chen, L., Gao, J. et al. Nutritive/non-nutritive sweeteners and high fat diet contribute to dysregulation of sweet taste receptors and metabolic derangements in oral, intestinal and central nervous tissues. Eur J Nutr 62, 3149–3159 (2023). https://doi.org/10.1007/s00394-023-03187-9

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