Role of Fermented Goat Milk on Liver Gene and Protein Profiles Related to Iron Metabolism during Anemia Recovery

Inmaculada López-Aliaga,Javier Díaz-Castro,María J M Alférez,Jorge Moreno-Fernandez

doi:10.3390/nu12051336

Abstract

Despite the crucial role of the liver as the central regulator of iron homeostasis, no studies have directly tested the modulation of liver gene and protein expression patterns during iron deficiency instauration and recovery with fermented milks. Fermented goat milk consumption improves the key proteins of intestinal iron metabolism during iron deficiency recovery, enhancing the digestive and metabolic utilization of iron. The aim of this study was to assess the influence of fermented goat or cow milk consumption on liver iron homeostasis during iron-deficiency anemia recovery with normal or iron-overload diets. Analysis included iron status biomarkers, gene and protein expression in hepatocytes. In general, fermented goat milk consumption either with normal or high iron content up-regulated liver DMT1, FPN1 and FTL1 gene expression and DMT1 and FPN1 protein expression. However, HAMP mRNA expression was lower in all groups of animals fed fermented goat milk. Additionally, hepcidin protein expression decreased in control and anemic animals fed fermented goat milk with normal iron content. In conclusion, fermented goat milk potentiates the up-regulation of key genes coding for proteins involved in iron metabolism, such as DMT1, and FPN1, FTL1 and down-regulation of HAMP, playing a key role in enhanced iron repletion during anemia recovery, inducing a physiological adaptation of the liver key genes and proteins coordinated with the fluctuation of the cellular iron levels, favoring whole-body iron homeostasis.

Highlights

Iron deficiency anemia (IDA) is a highly prevalent pathology and a medical condition in the clinical practice, affecting more than two billion people worldwide
Taking into account all these considerations, the aim of this study was to contribute to a better understanding of iron metabolism during IDA recovery, by studying how fermented goat vs. cow milk consumption affects liver iron homeostasis during nutritional iron repletion in animal models with severe, induced iron-deficiency anemia and overload
Iron deprivation impaired all the hematological parameters studied [9], and these parameters are detailed in Supplementary Table S1

Summary

Introduction

Iron deficiency anemia (IDA) is a highly prevalent pathology and a medical condition in the clinical practice, affecting more than two billion people worldwide. This public health problem has a negative impact on the lives of infants and fertile women worldwide [1]. The non-heme iron in the diet is in Fe3+ form and it must be reduced to ferrous form before it can be absorbed by the action of duodenal cytochrome B. This protein transports some divalent cations including ferrous iron. Iron crosses the basolateral membrane of intestinal enterocytes by the action of ferroportin, an iron exporter, entering into systemic circulation. The mechanisms regulating systemic iron homeostasis are largely centered on the Nutrients 2020, 12, 1336; doi:10.3390/nu12051336 www.mdpi.com/journal/nutrients

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