Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases
ObjectiveZinc is an essential micronutrient that is critical for many physiological processes, including glucose metabolism, regulation of inflammation, and intestinal barrier function. Further, zinc dysregulation is associated with an increased risk of chronic inflammatory diseases such as type II...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2023.1220533/full |
| _version_ | 1797744821805252608 |
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| author | Samuel Blake Mitchell Yu-Han Hung Yu-Han Hung Trista Lee Thorn Jiaqi Zou Filiz Baser Sukru Gulec Celeste Cheung Tolunay Beker Aydemir |
| author_facet | Samuel Blake Mitchell Yu-Han Hung Yu-Han Hung Trista Lee Thorn Jiaqi Zou Filiz Baser Sukru Gulec Celeste Cheung Tolunay Beker Aydemir |
| author_sort | Samuel Blake Mitchell |
| collection | DOAJ |
| description | ObjectiveZinc is an essential micronutrient that is critical for many physiological processes, including glucose metabolism, regulation of inflammation, and intestinal barrier function. Further, zinc dysregulation is associated with an increased risk of chronic inflammatory diseases such as type II diabetes, obesity, and inflammatory bowel disease. However, whether altered zinc status is a symptom or cause of disease onset remains unclear. Common symptoms of these three chronic diseases include the onset of increased intestinal permeability and zinc dyshomeostasis. The specific focus of this work is to investigate how dietary sources of intestinal permeability, such as high sucrose consumption, impact transporter-mediated zinc homeostasis and subsequent zinc-dependent physiology contributing to disease development.MethodWe used in vivo subchronic sucrose treatment, ex vivo intestinal organoid culture, and in vitro cell systems. We analyze the alterations in zinc metabolism and intestinal permeability and metabolic outcomes.ResultsWe found that subchronic sucrose treatment resulted in systemic changes in steady-state zinc distribution and increased 65Zn transport (blood-to-intestine) along with greater ZIP14 expression at the basolateral membrane of the intestine. Further, sucrose treatment enhanced cell survival of intestinal epithelial cells, activation of the EGFR-AKT-STAT3 pathway, and intestinal permeability.ConclusionOur work suggests that subchronic high sucrose consumption alters systemic and intestinal zinc homeostasis linking diet-induced changes in zinc homeostasis to the intestinal permeability and onset of precursors for chronic disease. |
| first_indexed | 2024-03-12T15:14:47Z |
| format | Article |
| id | doaj.art-2d0baeb040c942daa3db8050f9b675fa |
| institution | Directory Open Access Journal |
| issn | 2296-861X |
| language | English |
| last_indexed | 2024-03-12T15:14:47Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-2d0baeb040c942daa3db8050f9b675fa2023-08-11T14:56:53ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2023-08-011010.3389/fnut.2023.12205331220533Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseasesSamuel Blake Mitchell0Yu-Han Hung1Yu-Han Hung2Trista Lee Thorn3Jiaqi Zou4Filiz Baser5Sukru Gulec6Celeste Cheung7Tolunay Beker Aydemir8Division of Nutritional Sciences, Cornell University, Ithaca, NY, United StatesDivision of Nutritional Sciences, Cornell University, Ithaca, NY, United StatesCollege of Veterinary Medicine, Cornell University, Ithaca, NY, United StatesDivision of Nutritional Sciences, Cornell University, Ithaca, NY, United StatesDivision of Nutritional Sciences, Cornell University, Ithaca, NY, United StatesMolecular Nutrition and Human Physiology Laboratory, Department of Food Engineering, İzmir Institute of Technology, İzmir, TürkiyeMolecular Nutrition and Human Physiology Laboratory, Department of Food Engineering, İzmir Institute of Technology, İzmir, TürkiyeDivision of Nutritional Sciences, Cornell University, Ithaca, NY, United StatesDivision of Nutritional Sciences, Cornell University, Ithaca, NY, United StatesObjectiveZinc is an essential micronutrient that is critical for many physiological processes, including glucose metabolism, regulation of inflammation, and intestinal barrier function. Further, zinc dysregulation is associated with an increased risk of chronic inflammatory diseases such as type II diabetes, obesity, and inflammatory bowel disease. However, whether altered zinc status is a symptom or cause of disease onset remains unclear. Common symptoms of these three chronic diseases include the onset of increased intestinal permeability and zinc dyshomeostasis. The specific focus of this work is to investigate how dietary sources of intestinal permeability, such as high sucrose consumption, impact transporter-mediated zinc homeostasis and subsequent zinc-dependent physiology contributing to disease development.MethodWe used in vivo subchronic sucrose treatment, ex vivo intestinal organoid culture, and in vitro cell systems. We analyze the alterations in zinc metabolism and intestinal permeability and metabolic outcomes.ResultsWe found that subchronic sucrose treatment resulted in systemic changes in steady-state zinc distribution and increased 65Zn transport (blood-to-intestine) along with greater ZIP14 expression at the basolateral membrane of the intestine. Further, sucrose treatment enhanced cell survival of intestinal epithelial cells, activation of the EGFR-AKT-STAT3 pathway, and intestinal permeability.ConclusionOur work suggests that subchronic high sucrose consumption alters systemic and intestinal zinc homeostasis linking diet-induced changes in zinc homeostasis to the intestinal permeability and onset of precursors for chronic disease.https://www.frontiersin.org/articles/10.3389/fnut.2023.1220533/fullpermeabilitybarrier functionzinc transporterZIP14Slc39a14glucose |
| spellingShingle | Samuel Blake Mitchell Yu-Han Hung Yu-Han Hung Trista Lee Thorn Jiaqi Zou Filiz Baser Sukru Gulec Celeste Cheung Tolunay Beker Aydemir Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases Frontiers in Nutrition permeability barrier function zinc transporter ZIP14 Slc39a14 glucose |
| title | Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases |
| title_full | Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases |
| title_fullStr | Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases |
| title_full_unstemmed | Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases |
| title_short | Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases |
| title_sort | sucrose induced hyperglycemia dysregulates intestinal zinc metabolism and integrity risk factors for chronic diseases |
| topic | permeability barrier function zinc transporter ZIP14 Slc39a14 glucose |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2023.1220533/full |
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