PMID- 31510077
OWN - NLM
STAT- MEDLINE
DCOM- 20200225
LR  - 20211204
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 11
IP  - 9
DP  - 2019 Sep 10
TI  - A Low Iron Diet Protects from Steatohepatitis in a Mouse Model.
LID - 10.3390/nu11092172 [doi]
LID - 2172
AB  - High tissue iron levels are a risk factor for multiple chronic diseases including 
      type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). To 
      investigate causal relationships and underlying mechanisms, we used an 
      established NAFLD model-mice fed a high fat diet with supplemental fructose in 
      the water ("fast food", FF). Iron did not affect excess hepatic triglyceride 
      accumulation in the mice on FF, and FF did not affect iron accumulation compared 
      to normal chow. Mice on low iron are protected from worsening of markers for 
      non-alcoholic steatohepatitis (NASH), including serum transaminases and fibrotic 
      gene transcript levels. These occurred prior to the onset of significant insulin 
      resistance or changes in adipokines. Transcriptome sequencing revealed the major 
      effects of iron to be on signaling by the transforming growth factor beta (TGF-beta) 
      pathway, a known mechanistic factor in NASH. High iron increased fibrotic gene 
      expression in vitro, demonstrating that the effect of dietary iron on NASH is 
      direct. Conclusion: A lower tissue iron level prevents accelerated progression of 
      NAFLD to NASH, suggesting a possible therapeutic strategy in humans with the 
      disease.
FAU - Salaye, Lipika
AU  - Salaye L
AUID- ORCID: 0000-0001-5256-6565
AD  - Center on Diabetes, Obesity and Metabolism, Department of Internal Medicine, Wake 
      Forest Baptist Medical Center, Winston-Salem, NC 27101, USA.
FAU - Bychkova, Ielizaveta
AU  - Bychkova I
AD  - Department of Internal Medicine, University of Utah Medical Center, Salt Lake 
      City, UT 84112, USA.
FAU - Sink, Sandy
AU  - Sink S
AD  - Center on Diabetes, Obesity and Metabolism, Department of Internal Medicine, Wake 
      Forest Baptist Medical Center, Winston-Salem, NC 27101, USA.
FAU - Kovalic, Alexander J
AU  - Kovalic AJ
AD  - Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, 
      NC 27157, USA.
FAU - Bharadwaj, Manish S
AU  - Bharadwaj MS
AD  - Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC 27157, 
      USA.
AD  - Agilent Technologies, 121 Hartwell Ave, Lexington, MA 02421, USA.
FAU - Lorenzo, Felipe
AU  - Lorenzo F
AD  - Center on Diabetes, Obesity and Metabolism, Department of Internal Medicine, Wake 
      Forest Baptist Medical Center, Winston-Salem, NC 27101, USA.
FAU - Jain, Shalini
AU  - Jain S
AD  - Center on Diabetes, Obesity and Metabolism, Department of Internal Medicine, Wake 
      Forest Baptist Medical Center, Winston-Salem, NC 27101, USA.
FAU - Harrison, Alexandria V
AU  - Harrison AV
AD  - Center on Diabetes, Obesity and Metabolism, Department of Internal Medicine, Wake 
      Forest Baptist Medical Center, Winston-Salem, NC 27101, USA.
FAU - Davis, Ashley T
AU  - Davis AT
AD  - Department of Comparative Medicine, Wake Forest University, Winston-Salem, NC 
      27157, USA.
FAU - Turnbull, Katherine
AU  - Turnbull K
AD  - Center on Diabetes, Obesity and Metabolism, Department of Internal Medicine, Wake 
      Forest Baptist Medical Center, Winston-Salem, NC 27101, USA.
AD  - Department of Comparative Medicine, Wake Forest University, Winston-Salem, NC 
      27157, USA.
FAU - Meegalla, Nuwan T
AU  - Meegalla NT
AD  - Center on Diabetes, Obesity and Metabolism, Department of Internal Medicine, Wake 
      Forest Baptist Medical Center, Winston-Salem, NC 27101, USA.
AD  - Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, 
      NC 27157, USA.
FAU - Lee, Soh-Hyun
AU  - Lee SH
AUID- ORCID: 0000-0001-6620-8961
AD  - Department of Internal Medicine, University of Utah Medical Center, Salt Lake 
      City, UT 84112, USA.
FAU - Cooksey, Robert
AU  - Cooksey R
AD  - Department of Internal Medicine, University of Utah Medical Center, Salt Lake 
      City, UT 84112, USA.
AD  - VA Medical Center, Salt Lake City, UT 84148, USA.
FAU - Donati, George L
AU  - Donati GL
AUID- ORCID: 0000-0002-3686-5327
AD  - Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA.
FAU - Kavanagh, Kylie
AU  - Kavanagh K
AUID- ORCID: 0000-0001-8772-6186
AD  - Department of Comparative Medicine, Wake Forest University, Winston-Salem, NC 
      27157, USA.
AD  - Department of Biomedicine, University of Tasmania, Hobart, Tasmania 7000, 
      Australia.
FAU - Bonkovsky, Herbert L
AU  - Bonkovsky HL
AD  - Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, 
      NC 27157, USA.
FAU - McClain, Donald A
AU  - McClain DA
AD  - Center on Diabetes, Obesity and Metabolism, Department of Internal Medicine, Wake 
      Forest Baptist Medical Center, Winston-Salem, NC 27101, USA. 
      dmcclain@wakehealth.edu.
AD  - VA Medical Center, Salt Lake City, UT 84148, USA. dmcclain@wakehealth.edu.
AD  - VA Medical Center, Salisbury, NC 28144, USA. dmcclain@wakehealth.edu.
LA  - eng
GR  - P30 CA012197/CA/NCI NIH HHS/United States
GR  - T35 OD010946/OD/NIH HHS/United States
GR  - 5R01DK081842, DAM; 5UL1 TR001420, DAM/NH/NIH HHS/United States
GR  - 2I01 BX001140, DAM/Research Service of the Department of Veterans Affairs/
PT  - Journal Article
DEP - 20190910
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Iron, Dietary)
RN  - 30237-26-4 (Fructose)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animal Feed
MH  - Animals
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Fructose
MH  - Gene Expression Regulation
MH  - Hep G2 Cells
MH  - Humans
MH  - Iron/blood
MH  - *Iron Deficiencies
MH  - Iron, Dietary/*administration & dosage/blood
MH  - Liver/*metabolism/pathology
MH  - Liver Cirrhosis/blood/genetics/pathology/*prevention & control
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Non-alcoholic Fatty Liver Disease/blood/genetics/pathology/*prevention & control
MH  - Signal Transduction
PMC - PMC6769937
OTO - NOTNLM
OT  - NAFLD
OT  - RNA-seq
OT  - iron
OT  - metabolic syndrome
COIS- The authors declare no conflict of interest.
EDAT- 2019/09/13 06:00
MHDA- 2020/02/26 06:00
PMCR- 2019/09/01
CRDT- 2019/09/13 06:00
PHST- 2019/08/11 00:00 [received]
PHST- 2019/08/31 00:00 [revised]
PHST- 2019/09/06 00:00 [accepted]
PHST- 2019/09/13 06:00 [entrez]
PHST- 2019/09/13 06:00 [pubmed]
PHST- 2020/02/26 06:00 [medline]
PHST- 2019/09/01 00:00 [pmc-release]
AID - nu11092172 [pii]
AID - nutrients-11-02172 [pii]
AID - 10.3390/nu11092172 [doi]
PST - epublish
SO  - Nutrients. 2019 Sep 10;11(9):2172. doi: 10.3390/nu11092172.