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

Jorge Moreno-Fernandez, María J M Alférez, Inmaculada López-Aliaga, Javier Díaz-Castro
Author Information
  1. Jorge Moreno-Fernandez: Department of Physiology, University of Granada, 18071 Granada, Spain. ORCID
  2. María J M Alférez: Department of Physiology, University of Granada, 18071 Granada, Spain. ORCID
  3. Inmaculada López-Aliaga: Department of Physiology, University of Granada, 18071 Granada, Spain.
  4. Javier Díaz-Castro: Department of Physiology, University of Granada, 18071 Granada, Spain. ORCID

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.

Keywords

References

  1. Blood. 2011 Apr 28;117(17):4425-33 [PMID: 21346250]
  2. Cell. 2017 Jan 26;168(3):344-361 [PMID: 28129536]
  3. Mol Metab. 2019 Jun;24:64-79 [PMID: 30954544]
  4. Gut. 2000 Feb;46(2):270-6 [PMID: 10644324]
  5. J Dairy Sci. 2014;97(1):147-54 [PMID: 24239078]
  6. Curr Opin Chem Biol. 2020 Apr;55:34-44 [PMID: 31918395]
  7. Br J Nutr. 1993 Sep;70(2):609-20 [PMID: 8260485]
  8. Br J Haematol. 1994 Jan;86(1):156-62 [PMID: 8011525]
  9. Nutrients. 2018 Aug 27;10(9): [PMID: 30150549]
  10. J Nutr. 2005 Jan;135(1):27-32 [PMID: 15623828]
  11. J Dairy Res. 2015 Feb;82(1):86-94 [PMID: 25394837]
  12. Pharmacol Res. 2017 Jan;115:242-254 [PMID: 27867027]
  13. Blood. 2003 Apr 1;101(7):2461-3 [PMID: 12433676]
  14. Clin Biochem Rev. 2016 May;37(2):51-62 [PMID: 28303071]
  15. Food Funct. 2018 Jun 20;9(6):3195-3201 [PMID: 29872815]
  16. J Agric Food Chem. 2017 May 24;65(20):4057-4065 [PMID: 28475318]
  17. Public Health Nutr. 2009 Apr;12(4):444-54 [PMID: 18498676]
  18. J Biol Chem. 2017 Aug 4;292(31):12735-12743 [PMID: 28615441]
  19. Hepatology. 2015 Apr;61(4):1306-20 [PMID: 25475192]
  20. J Agric Food Chem. 2016 Mar 30;64(12):2560-8 [PMID: 26976781]
  21. J Nutr. 1993 Nov;123(11):1939-51 [PMID: 8229312]
  22. Ann Clin Biochem. 2017 Jan;54(1):43-48 [PMID: 27701066]
  23. Nutrients. 2019 Mar 15;11(3): [PMID: 30875895]
  24. Br J Nutr. 2012 Jul 14;108(1):1-8 [PMID: 22018161]
  25. N Engl J Med. 2005 Mar 10;352(10):1011-23 [PMID: 15758012]
  26. Food Chem. 2014 Feb 15;145:1097-105 [PMID: 24128590]
  27. Cell. 2010 Jul 9;142(1):24-38 [PMID: 20603012]
  28. Am J Physiol Gastrointest Liver Physiol. 2017 Sep 1;313(3):G157-G165 [PMID: 28596277]
  29. Antioxid Redox Signal. 2014 Apr 10;20(11):1754-69 [PMID: 24124891]
  30. Cell Metab. 2012 Jun 6;15(6):905-17 [PMID: 22682226]

Grants

  1. P11-AGR-7648/Junta de Andalucía

MeSH Term

Anemia, Iron-Deficiency
Animals
Apoferritins
Cation Transport Proteins
Cattle
Eating
Fermentation
Gene Expression
Goats
Hepcidins
Homeostasis
Humans
Intestinal Mucosa
Iron
Liver
Milk
Rats, Wistar
Ferroportin

Chemicals

Cation Transport Proteins
FTL protein, human
Hamp protein, rat
Hepcidins
Ferroportin
solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
Apoferritins
Iron

Word Cloud

Created with Highcharts 10.0.0ironexpressionfermentedgoatmilkliverproteinhomeostasisgenerecoverykeyconsumptionproteinsanemianormalDMT1FPN1roledeficiencyFermentedmetabolismcowcontentFTL1HAMPanimalsfedgenesrepletionDespitecrucialcentralregulatorstudiesdirectlytestedmodulationpatternsinstaurationmilksimprovesintestinalenhancingdigestivemetabolicutilizationaimstudyassessinfluenceiron-deficiencyiron-overloaddietsAnalysisincludedstatusbiomarkershepatocytesgeneraleitherhighup-regulatedHowevermRNAlowergroupsAdditionallyhepcidindecreasedcontrolanemicconclusionpotentiatesup-regulationcodinginvolveddown-regulationplayingenhancedinducingphysiologicaladaptationcoordinatedfluctuationcellularlevelsfavoringwhole-bodyRoleGoatMilkLiverGeneProteinProfilesRelatedIronMetabolismAnemiaRecovery

Similar Articles

Cited By

No available data.