Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
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Dietary zinc supplementation in high-fat diet-induced obese mice: Effects on the skeletal muscle ZIP7 expression and blood glucose regulation

고지방식이 유도 비만 마우스에서 아연 보충이 골격 근육의 아연 수송체 ZIP7 수준과 혈당 조절에 미치는 영향

  • Zhu, Qianjing (Department of Food and Nutrition, College of Human Ecology, Kyung Hee University) ;
  • Chung, Jayong (Department of Food and Nutrition, College of Human Ecology, Kyung Hee University)
  • 주치앤징 (경희대학교 생활과학대학 식품영양학과) ;
  • 정자용 (경희대학교 생활과학대학 식품영양학과)
  • Received : 2021.10.31
  • Accepted : 2021.11.26
  • Published : 2021.12.31
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Abstract

Purpose: The zinc transporter ZIP7 is known to regulate glucose metabolism in skeletal muscles, and skeletal muscles are known to play a critical role in glycemic control. The present study examines the effects of dietary zinc supplementation on the blood glucose concentration and expression of ZIP7 in skeletal muscle obtained from obese mice fed a high-fat diet (HF). Methods: C57BL/6J male mice were divided into three groups and were administered either a HF (60% of total calories from fat), HF supplemented with zinc (HF+Zn, 60% calories from fat + 300 mg zinc/kg diet), or low-fat diet (CON, 10% calories from fat), for 15 weeks. Results: Compared to CON group mice, the final body weights and adipose tissue weights were significantly increased, while the skeletal muscle weights were significantly decreased in mice belonging to the HF and HF+Zn groups. The HF+Zn group had significantly lower levels of fasting blood glucose concentrations than the HF group. Similarly, zinc supplementation significantly decreased the HF-elevated area under the curve values obtained from the oral glucose tolerance test. Skeletal muscle protein levels of ZIP7 in samples obtained from the HF group were significantly decreased as compared to the CON group. Conversely, the skeletal ZIP7 protein levels in the HF+Zn group were significantly increased as compared to the HF group. Moreover, the protein levels of phosphorylated-AKT and glucose transporter 4 in the skeletal muscle were significantly increased subsequent to zinc supplementation. Conclusion: Our data demonstrates that zinc supplementation up-regulates the skeletal muscle ZIP7 expression, which is associated with improved glucose tolerance in the obesity.

본 연구는 고지방식이로 유도한 비만 동물모델에서 아연의 식이를 통한 보충 급여가 혈당 조절과 골격 근육의 ZIP7의 작용에 미치는 영향에 대해 살펴보았다. 고지방식이를 공급한 HF군은 정상 대조군에 비하여 단위 체중당 골격 근육 무게가 유의하게 감소하였으며, 혈당은 유의적으로 증가하였다. 고지방식이와 함께 아연을 보충 공급한 HF+Zn군은 아연을 보충하지 않은 HF군과 비교하여, 공복 혈당과 경구 포도당 부하 후 혈당 증가 면적이 유의하게 감소하였다. 또한, HF+Zn군은 HF군에 비해 골격 근육의 ZIP7 단백질 수준이 유의하게 증가하였으며, AKT 활성과 GLUT4 단백질 수준도 유의하게 증가하는 것으로 나타났다. 이상의 결과를 종합해 볼 때, 아연 보충은 비만으로 인한 고혈당 증세를 완화하는 효과를 나타내며, 이는 골격 근육에서의 ZIP7 아연 수송체에 의한 당 대사 조절과 관련이 있을 것으로 생각된다.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF) funded by the Korean Government (MIST) (NRF-2020R1F1A1075611).

References

  1. World Health Organization. Obesity and overweight. Geneva; 2020.
  2. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest 2000; 106(4): 473-481. https://doi.org/10.1172/JCI10842
  3. Petersen KF, Dufour S, Savage DB, Bilz S, Solomon G, Yonemitsu S, et al. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci U S A 2007; 104(31):12587-12594. https://doi.org/10.1073/pnas.0705408104
  4. Fukunaka A, Fujitani Y. Role of zinc homeostasis in the pathogenesis of diabetes and obesity. Int J Mol Sci 2018; 19(2): 476. https://doi.org/10.3390/ijms19020476
  5. Vallee BL, Falchuk KH. The biochemical basis of zinc physiology. Physiol Rev 1993; 73(1): 79-118. https://doi.org/10.1152/physrev.1993.73.1.79
  6. Baltaci AK, Yuce K. Zinc transporter proteins. Neurochem Res 2018; 43(3): 517-530. https://doi.org/10.1007/s11064-017-2454-y
  7. Hara T, Takeda TA, Takagishi T, Fukue K, Kambe T, Fukada T. Physiological roles of zinc transporters: molecular and genetic importance in zinc homeostasis. J Physiol Sci 2017; 67(2): 283-301. https://doi.org/10.1007/s12576-017-0521-4
  8. de Luis DA, Pacheco D, Izaola O, Terroba MC, Cuellar L, Cabezas G. Micronutrient status in morbidly obese women before bariatric surgery. Surg Obes Relat Dis 2013; 9(2): 323-327. https://doi.org/10.1016/j.soard.2011.09.015
  9. El Dib R, Gameiro OL, Ogata MS, Modolo NS, Braz LG, Jorge EC, et al. Zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance. Cochrane Database Syst Rev 2015;(5): CD005525.
  10. Qi Y, Zhang Z, Liu S, Aluo Z, Zhang L, Yu L, et al. Zinc supplementation alleviates lipid and glucose metabolic disorders induced by a high-fat diet. J Agric Food Chem 2020; 68(18): 5189-5200. https://doi.org/10.1021/acs.jafc.0c01103
  11. Thoen RU, Barther NN, Schemitt E, Bona S, Fernandes S, Coral G, et al. Zinc supplementation reduces dietinduced obesity and improves insulin sensitivity in rats. Appl Physiol Nutr Metab 2019; 44(6): 580-586. https://doi.org/10.1139/apnm-2018-0519
  12. Myers SA, Nield A, Chew GS, Myers MA. The zinc transporter, Slc39a7 (Zip7) is implicated in glycaemic control in skeletal muscle cells. PLoS One 2013; 8(11): e79316. https://doi.org/10.1371/journal.pone.0079316
  13. Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 2003; 28(7): 916-931. https://doi.org/10.1016/S0306-4530(02)00108-7
  14. Huang L, Tepaamorndech S, Kirschke CP, Newman JW, Keyes WR, Pedersen TL, et al. Aberrant fatty acid metabolism in skeletal muscle contributes to insulin resistance in zinc transporter 7 (znt7)-knockout mice. J Biol Chem 2018; 293(20): 7549-7563. https://doi.org/10.1074/jbc.M117.817692
  15. Norouzi S, Adulcikas J, Henstridge DC, Sonda S, Sohal SS, Myers S. The zinc transporter Zip7 is downregulated in skeletal muscle of insulin-resistant cells and in mice fed a high-fat diet. Cells 2019; 8(7): 663. https://doi.org/10.3390/cells8070663
  16. Min B, Chung J. Effects of high-fat diet induced obesity on tissue zinc concentrations and zinc transporter expressions in mice. J Nutr Health 2018; 51(6): 489-497. https://doi.org/10.4163/jnh.2018.51.6.489
  17. Kennedy ML, Failla ML, Smith JC Jr. Influence of genetic obesity on tissue concentrations of zinc, copper, manganese and iron in mice. J Nutr 1986; 116(8): 1432-1441. https://doi.org/10.1093/jn/116.8.1432
  18. Tsao TS, Li J, Chang KS, Stenbit AE, Galuska D, Anderson JE, et al. Metabolic adaptations in skeletal muscle overexpressing GLUT4: effects on muscle and physical activity. FASEB J 2001; 15(6): 958-969. https://doi.org/10.1096/fsb2fj000381
  19. Mnatsakanyan H, Serra RSI, Rico P, Salmeron-Sanchez M. Zinc uptake promotes myoblast differentiation via Zip7 transporter and activation of Akt signalling transduction pathway. Sci Rep 2018; 8(1): 13642. https://doi.org/10.1038/s41598-018-32067-0
  20. Taylor KM, Vichova P, Jordan N, Hiscox S, Hendley R, Nicholson RI. ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer cells. Endocrinology 2008; 149(10): 4912-4920. https://doi.org/10.1210/en.2008-0351
  21. Nimmanon T, Ziliotto S, Morris S, Flanagan L, Taylor KM. Phosphorylation of zinc channel ZIP7 drives MAPK, PI3K and mTOR growth and proliferation signalling. Metallomics 2017; 9(5): 471-481. https://doi.org/10.1039/c6mt00286b