Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status: A study of the effects of zinc deficiency during lactation

Ayako Hashimoto, Miki Nakagawa, Natsuki Tsujimura, Shiho Miyazaki, Kumiko Kizu, Tomoko Goto, Yusuke Komatsu, Ayu Matsunaga, Hitoshi Shirakawa, Hiroshi Narita, Taiho Kambe, Michio Komai

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


Systemic and cellular zinc homeostasis is elaborately controlled by ZIP and ZnT zinc transporters. Therefore, detailed characterization of their expression properties is of importance. Of these transporter proteins, Zip4 functions as the primarily important transporter to control systemic zinc homeostasis because of its indispensable function of zinc absorption in the small intestine. In this study, we closely investigated Zip4 protein accumulation in the rat small intestine in response to zinc status using an anti-Zip4 monoclonal antibody that we generated and contrasted this with the zinc-responsive activity of the membrane-bound alkaline phosphatase (ALP). We found that Zip4 accumulation is more rapid in response to zinc deficiency than previously thought. Accumulation increased in the jejunum as early as 1 day following a zinc-deficient diet. In the small intestine, Zip4 protein expression was higher in the jejunum than in the duodenum and was accompanied by reduction of ALP activity, suggesting that the jejunum can become zinc deficient more easily. Furthermore, by monitoring Zip4 accumulation levels and ALP activity in the duodenum and jejunum, we reasserted that zinc deficiency during lactation may transiently alter plasma glucose levels in the offspring in a sex-specific manner, without affecting homeostatic control of zinc metabolism. This confirms that zinc nutrition during lactation is extremely important for the health of the offspring. These results reveal that rapid Zip4 accumulation provides a significant conceptual advance in understanding the molecular basis of systemic zinc homeostatic control, and that properties of Zip4 protein accumulation are useful to evaluate zinc status closely.

Original languageEnglish
Pages (from-to)R459-R468
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number5
Publication statusPublished - 2016 Mar


  • Alkaline phosphatase
  • Glucose homeostasis
  • Small intestine
  • Zinc deficiency
  • Zip4 processing

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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