PMID- 32629238
OWN - NLM
STAT- MEDLINE
DCOM- 20210531
LR  - 20220129
IS  - 1873-4847 (Electronic)
IS  - 0955-2863 (Print)
IS  - 0955-2863 (Linking)
VI  - 84
DP  - 2020 Oct
TI  - Development of insulin resistance preceded major changes in iron homeostasis in 
      mice fed a high-fat diet.
PG  - 108441
LID - S0955-2863(20)30473-3 [pii]
LID - 10.1016/j.jnutbio.2020.108441 [doi]
AB  - Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) have been associated 
      with dysregulation of iron metabolism. The basis for this association is not 
      completely understood. To attempt to investigate this, we studied temporal 
      associations between onset of insulin resistance (IR) and dysregulated iron 
      homeostasis, in a mouse model of T2DM. Male C57Bl/6 mice (aged 8 weeks) were fed 
      a high-fat diet (HFD; 60% energy from fat) or a control diet (CD; 10% energy from 
      fat) for 4, 8, 12, 16, 20 and 24 weeks. Development of IR was documented, and 
      various metabolic, inflammatory and iron-related parameters were studied in these 
      mice. HFD-feeding induced weight gain, hepato-steatosis and IR in the mice. Onset 
      of IR occurred from 12 weeks onwards. Hepatic iron stores progressively declined 
      from 16 weeks onwards. Accompanying changes included a decrease in hepatic 
      hepcidin (Hamp1) mRNA expression and serum hepcidin levels and an increase in 
      iron content in the epididymal white adipose tissue (eWAT). Iron content in the 
      liver negatively correlated with that in the eWAT. Factors known to regulate 
      hepatic Hamp1 expression (such as serum iron levels, systemic inflammation, and 
      bone marrow-derived erythroid regulators) were not affected by HFD-feeding. In 
      conclusion, the results show that the onset of IR in HFD-fed mice preceded 
      dysregulation of iron homeostasis, evidence of which were found both in the liver 
      and visceral adipose tissue.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Varghese, Joe
AU  - Varghese J
AD  - Department of Biochemistry, Christian Medical College, Vellore 632002, Tamil 
      Nadu, India. Electronic address: joevarghese@cmcvellore.ac.in.
FAU - James, Jithu V
AU  - James JV
AD  - Department of Biochemistry, Christian Medical College, Vellore 632002, Tamil 
      Nadu, India.
FAU - Anand, R
AU  - Anand R
AD  - Department of Biochemistry, Christian Medical College, Vellore 632002, Tamil 
      Nadu, India.
FAU - Narayanasamy, Muthuraman
AU  - Narayanasamy M
AD  - Department of Biochemistry, Christian Medical College, Vellore 632002, Tamil 
      Nadu, India.
FAU - Rebekah, Grace
AU  - Rebekah G
AD  - Department of Biostatistics, Christian Medical College, Vellore 632002, Tamil 
      Nadu, India.
FAU - Ramakrishna, Banumathi
AU  - Ramakrishna B
AD  - Department of Pathology, Christian Medical College, Vellore 632002, Tamil Nadu, 
      India.
FAU - Nellickal, Arun Jose
AU  - Nellickal AJ
AD  - Department of Clinical Biochemistry, Christian Medical College, Vellore 632002, 
      Tamil Nadu, India(3).
FAU - Jacob, Molly
AU  - Jacob M
AD  - Department of Biochemistry, Christian Medical College, Vellore 632002, Tamil 
      Nadu, India. Electronic address: mjacob@cmcvellore.ac.in.
LA  - eng
GR  - 500190-Z-11-Z/WTDBT_/DBT-Wellcome Trust India Alliance/India
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200602
PL  - United States
TA  - J Nutr Biochem
JT  - The Journal of nutritional biochemistry
JID - 9010081
RN  - 0 (Insulin)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - Diabetes Mellitus, Type 2/metabolism
MH  - Diet, High-Fat/*adverse effects
MH  - Homeostasis
MH  - Inflammation/metabolism
MH  - Insulin/*metabolism
MH  - *Insulin Resistance
MH  - Iron/*metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
PMC - PMC7115812
MID - EMS86789
OTO - NOTNLM
OT  - Adipose tissue iron
OT  - Hepatic iron content
OT  - Hepcidin
OT  - High-fat diet
OT  - Insulin resistance
OT  - Iron
COIS- Declaration of competing interest The authors have no conflicts of interest to 
      declare.
EDAT- 2020/07/07 06:00
MHDA- 2021/06/01 06:00
PMCR- 2020/07/23
CRDT- 2020/07/07 06:00
PHST- 2019/05/15 00:00 [received]
PHST- 2020/03/10 00:00 [revised]
PHST- 2020/05/22 00:00 [accepted]
PHST- 2020/07/07 06:00 [pubmed]
PHST- 2021/06/01 06:00 [medline]
PHST- 2020/07/07 06:00 [entrez]
PHST- 2020/07/23 00:00 [pmc-release]
AID - S0955-2863(20)30473-3 [pii]
AID - 10.1016/j.jnutbio.2020.108441 [doi]
PST - ppublish
SO  - J Nutr Biochem. 2020 Oct;84:108441. doi: 10.1016/j.jnutbio.2020.108441. Epub 2020 
      Jun 2.