Milk osteopontin mediates zinc uptake in intestinal cells in the presence of phytic acid

Brian Christensen; Thomas F. Krüger; Thilde P. Hjorth; Emilie Holkgaard Buhl; Esben S. Sørensen

doi:10.1016/j.idairyj.2024.106113

Milk osteopontin mediates zinc uptake in intestinal cells in the presence of phytic acid

Brian Christensen, Thomas F. Krüger, Thilde P. Hjorth, Emilie Holkgaard Buhl, Esben S. Sørensen^*

^*Corresponding author for this work

Department of Molecular Biology and Genetics - Cellular Health, Intervention, and Nutrition

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

1 Citation (Scopus)

Abstract

The bioavailability and the intestinal absorption of the essential mineral zinc are challenged by the food matrix and especially the content of zinc chelating antinutrients. Many milk proteins and peptides affect zinc bioavailability. Osteopontin (OPN) is an acidic and highly phosphorylated whey protein that has been shown to bind calcium, magnesium and iron. Here we report the zinc binding properties of OPN, and the effect of OPN-Zn complexes on zinc absorption in Caco-2 cells. By isothermal titration calorimetry milk OPN was shown to bind approximately 36 zinc ions (K_D of ∼70 μM). The binding was mainly mediated by the phosphorylations in the protein. OPN retained zinc bound after in vitro simulated gastrointestinal transit. Interestingly the OPN-Zn complex enhanced zinc bioavailability in the presence of phytic acid, compared to inorganic zinc salts. Zinc uptake mediated by OPN significantly upregulated the gene expression of MT1G and ZnT1 which are crucial proteins involved in preserving enterocyte zinc homoeostasis. These results indicate that OPN could be incorporated into functional foods and infant formulas to increase zinc bioavailability and uptake.

Original language	English
Article number	106113
Journal	International Dairy Journal
Volume	161
ISSN	0958-6946
DOIs	https://doi.org/10.1016/j.idairyj.2024.106113
Publication status	Published - Feb 2025

Keywords

Bioavailability
Caco-2 cells
Osteopontin
Zinc absorption
Zinc binding

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10.1016/j.idairyj.2024.106113

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title = "Milk osteopontin mediates zinc uptake in intestinal cells in the presence of phytic acid",

abstract = "The bioavailability and the intestinal absorption of the essential mineral zinc are challenged by the food matrix and especially the content of zinc chelating antinutrients. Many milk proteins and peptides affect zinc bioavailability. Osteopontin (OPN) is an acidic and highly phosphorylated whey protein that has been shown to bind calcium, magnesium and iron. Here we report the zinc binding properties of OPN, and the effect of OPN-Zn complexes on zinc absorption in Caco-2 cells. By isothermal titration calorimetry milk OPN was shown to bind approximately 36 zinc ions (KD of ∼70 μM). The binding was mainly mediated by the phosphorylations in the protein. OPN retained zinc bound after in vitro simulated gastrointestinal transit. Interestingly the OPN-Zn complex enhanced zinc bioavailability in the presence of phytic acid, compared to inorganic zinc salts. Zinc uptake mediated by OPN significantly upregulated the gene expression of MT1G and ZnT1 which are crucial proteins involved in preserving enterocyte zinc homoeostasis. These results indicate that OPN could be incorporated into functional foods and infant formulas to increase zinc bioavailability and uptake.",

keywords = "Bioavailability, Caco-2 cells, Osteopontin, Zinc absorption, Zinc binding",

author = "Brian Christensen and Kr{\"u}ger, {Thomas F.} and Hjorth, {Thilde P.} and Buhl, {Emilie Holkgaard} and S{\o}rensen, {Esben S.}",

year = "2025",

month = feb,

doi = "10.1016/j.idairyj.2024.106113",

language = "English",

volume = "161",

journal = "International Dairy Journal",

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TY - JOUR

T1 - Milk osteopontin mediates zinc uptake in intestinal cells in the presence of phytic acid

AU - Christensen, Brian

AU - Krüger, Thomas F.

AU - Hjorth, Thilde P.

AU - Buhl, Emilie Holkgaard

AU - Sørensen, Esben S.

PY - 2025/2

Y1 - 2025/2

N2 - The bioavailability and the intestinal absorption of the essential mineral zinc are challenged by the food matrix and especially the content of zinc chelating antinutrients. Many milk proteins and peptides affect zinc bioavailability. Osteopontin (OPN) is an acidic and highly phosphorylated whey protein that has been shown to bind calcium, magnesium and iron. Here we report the zinc binding properties of OPN, and the effect of OPN-Zn complexes on zinc absorption in Caco-2 cells. By isothermal titration calorimetry milk OPN was shown to bind approximately 36 zinc ions (KD of ∼70 μM). The binding was mainly mediated by the phosphorylations in the protein. OPN retained zinc bound after in vitro simulated gastrointestinal transit. Interestingly the OPN-Zn complex enhanced zinc bioavailability in the presence of phytic acid, compared to inorganic zinc salts. Zinc uptake mediated by OPN significantly upregulated the gene expression of MT1G and ZnT1 which are crucial proteins involved in preserving enterocyte zinc homoeostasis. These results indicate that OPN could be incorporated into functional foods and infant formulas to increase zinc bioavailability and uptake.

AB - The bioavailability and the intestinal absorption of the essential mineral zinc are challenged by the food matrix and especially the content of zinc chelating antinutrients. Many milk proteins and peptides affect zinc bioavailability. Osteopontin (OPN) is an acidic and highly phosphorylated whey protein that has been shown to bind calcium, magnesium and iron. Here we report the zinc binding properties of OPN, and the effect of OPN-Zn complexes on zinc absorption in Caco-2 cells. By isothermal titration calorimetry milk OPN was shown to bind approximately 36 zinc ions (KD of ∼70 μM). The binding was mainly mediated by the phosphorylations in the protein. OPN retained zinc bound after in vitro simulated gastrointestinal transit. Interestingly the OPN-Zn complex enhanced zinc bioavailability in the presence of phytic acid, compared to inorganic zinc salts. Zinc uptake mediated by OPN significantly upregulated the gene expression of MT1G and ZnT1 which are crucial proteins involved in preserving enterocyte zinc homoeostasis. These results indicate that OPN could be incorporated into functional foods and infant formulas to increase zinc bioavailability and uptake.

KW - Bioavailability

KW - Caco-2 cells

KW - Osteopontin

KW - Zinc absorption

KW - Zinc binding

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U2 - 10.1016/j.idairyj.2024.106113

DO - 10.1016/j.idairyj.2024.106113

M3 - Journal article

AN - SCOPUS:85207056581

SN - 0958-6946

VL - 161

JO - International Dairy Journal

JF - International Dairy Journal

M1 - 106113

ER -

Milk osteopontin mediates zinc uptake in intestinal cells in the presence of phytic acid

Abstract

Keywords

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