2. Academic Validation
  3. A dual absorption pathway of novel oyster-derived peptide-zinc complex enhances zinc bioavailability and restores mitochondrial function

A dual absorption pathway of novel oyster-derived peptide-zinc complex enhances zinc bioavailability and restores mitochondrial function

  • J Adv Res. 2025 Feb 13:S2090-1232(25)00077-3. doi: 10.1016/j.jare.2025.02.005.
Ximing Yang 1,  Siyi Wang 1,  Hanxiong Liu 1,  Tuo Zhang 2,  Shuzhen Cheng 3,  Ming Du 4
Affiliations

Affiliations

  • 1 SKL of Marine Food Processing & Safety Control, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China; National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China.
  • 2 College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
  • 3 SKL of Marine Food Processing & Safety Control, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China; National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China. Electronic address: chengshuzhen0547@yeah.net.
  • 4 SKL of Marine Food Processing & Safety Control, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China; National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China. Electronic address: duming@dlpu.edu.cn.
PMID: 39955018 DOI: 10.1016/j.jare.2025.02.005
Abstract

Zinc deficiency is a global health issue that impairs immune function, growth, and energy metabolism. Although conventional zinc supplements have been developed, their effectiveness is limited by poor bioavailability and susceptibility to dietary inhibitors. In this study, a peptide-zinc complex (IE-Zn) derived from oysters was developed to enhance zinc uptake and address metabolic disruptions caused by deficiency. It was determined that Zn2+ binds with high affinity to the IE peptide, promoting structural flexibility that facilitates zinc transport through both zinc ion transporters and oligopeptide transporters. In Caco-2 and IEC-6 cell models, IE-Zn was shown to significantly improve zinc absorption and retention compared to ZnSO4, driven by the upregulation of ZIP4 and PEPT1 transporters. In vivo studies in a zinc-deficient mouse model confirmed enhanced zinc absorption and distribution across serum, intestine, and liver. Moreover, IE-Zn restored energy homeostasis by activating the AMPK/PGC1-α/NRF-1/TFAM signaling pathway, promoting mitochondrial biogenesis and reducing oxidative stress. These findings suggest that IE-Zn is a superior zinc supplement with higher bioavailability and serves as a potent regulator of cellular energy metabolism, offering therapeutic potential for managing conditions related to zinc deficiency and mitochondrial dysfunction. This study lays the foundation for further exploration of peptide-mineral complexes as advanced nutritional supplements with broad applications. Subsequent studies will further investigate the absorption pathway and targeting of peptide-zinc complex. The hope is to provide potential preventive applications for people in need, including zinc deficiency and a range of diseases caused by zinc deficiency.

Keywords

AMPK/PGC1-α/NRF-1/TFAM signaling pathway; Dual absorption pathways; Mitochondrial function; Peptide-zinc complex; Zinc bioavailability.

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