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

Abstract

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.

Zinc deficiency causes delayed ATP clearance and adenosine generation in rats and cell culture models

“…After acclimation, the rats were divided into three groups and fed one of these diets for 4 days: Zn-Def, Zn-Low, and Zn-Suf diets, which contained 2.2, 4.1, and 33.7 mg zinc per kg, respectively 53 (Experiment 1). In another experiment, the rats were divided into four groups, after which they were allowed to acclimate for 4 days and fed one of these diets for 10 days: 4.0, 6.0, 8.0, and 33.7 mg zinc per kg diets (Experiment 2).…”

Orexigenic action of oral zinc: metabolomic analysis in the rat hypothalamus

“…In the case of early zinc signaling, an extracellular stimulus directly induces elevated zinc levels within several minutes by releasing zinc from the endoplasmic reticulum or from metallothionein. In this experiment, however, ZIP4 expression in the small intestinal mucosa must be increased because 2 days after the Zn-deficient diet feeding to the rat, which means 1 oral administration of Zn solution could be absorbed efficiently as reported previously [29]. Therefore, absorbed Zn might be increased in the small intestinal cells and move to the blood circulation, so this free Zn 2+ signaling may contribute to this mechanism, possibly through blood circulation or gastrointestinal vagus nerve signal transduction to the hypothalamus.…”

The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the hippocampus

“…[22][23][24] Because zinc deprivation Data are expressed as mean ± SD, n = 10. [25][26][27] Hence, the ALP activity is a good indicator to evaluate the status of zinc deficiency in growing rats. † Difference from the PF group, P < 0.05.…”