PMID- 25550467
OWN - NLM
STAT- MEDLINE
DCOM- 20150622
LR  - 20150402
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 29
IP  - 4
DP  - 2015 Apr
TI  - Cytosolic aconitase activity sustains adipogenic capacity of adipose tissue 
      connecting iron metabolism and adipogenesis.
PG  - 1529-39
LID - 10.1096/fj.14-258996 [doi]
AB  - To gain insight into the regulation of intracellular iron homeostasis in adipose 
      tissue, we investigated the role of iron regulatory protein 1/cytosolic aconitase 
      1 (ACO1). ACO1 gene expression and activity increased in parallel to expression 
      of adipogenic genes during differentiation of both murine 3T3-L1 cells and human 
      preadipocytes. Lentiviral knockdown (KD) of Aco1 in 3T3-L1 preadipocytes led to 
      diminished cytosolic aconitase activity and isocitrate dehydrogenase 1 (NADP(+)), 
      soluble (Idh1) mRNA levels, decreased intracellular NADPH:NADP ratio, and 
      impaired adipogenesis during adipocyte differentiation. In addition, Aco1 KD in 
      fully differentiated 3T3-L1 adipocytes decreased lipogenic, Idh1, Adipoq, and 
      Glut4 gene expression. A bidirectional cross-talk was found between intracellular 
      iron levels and ACO1 gene expression and protein activity. Although iron in 
      excess, known to increase reactive oxygen species production, and iron depletion 
      both resulted in decreased ACO1 mRNA levels and activity, Aco1 KD led to reduced 
      gene expression of transferrin receptor (Tfrc) and transferrin, disrupting 
      intracellular iron uptake. In agreement with these findings, in 2 human 
      independent cohorts (n = 85 and n = 38), ACO1 gene expression was positively 
      associated with adipogenic markers in subcutaneous and visceral adipose tissue. 
      ACO1 gene expression was also positively associated with the gene expression of 
      TFRC while negatively linked to ferroportin (solute carrier family 40 
      (iron-regulated transporter), member 1) mRNA levels. Altogether, these results 
      suggest that ACO1 activity is required for the normal adipogenic capacity of 
      adipose tissue by connecting iron, energy metabolism, and adipogenesis.
CI  - (c) FASEB.
FAU - Moreno, Maria
AU  - Moreno M
AD  - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio 
      Biomedica de Girona, CIBEROBN (CB06/03/010), and Instituto de Salud Carlos III, 
      Girona, Spain.
FAU - Ortega, Francisco
AU  - Ortega F
AD  - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio 
      Biomedica de Girona, CIBEROBN (CB06/03/010), and Instituto de Salud Carlos III, 
      Girona, Spain.
FAU - Xifra, Gemma
AU  - Xifra G
AD  - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio 
      Biomedica de Girona, CIBEROBN (CB06/03/010), and Instituto de Salud Carlos III, 
      Girona, Spain.
FAU - Ricart, Wifredo
AU  - Ricart W
AD  - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio 
      Biomedica de Girona, CIBEROBN (CB06/03/010), and Instituto de Salud Carlos III, 
      Girona, Spain.
FAU - Fernandez-Real, Jose Manuel
AU  - Fernandez-Real JM
AD  - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio 
      Biomedica de Girona, CIBEROBN (CB06/03/010), and Instituto de Salud Carlos III, 
      Girona, Spain.
FAU - Moreno-Navarrete, Jose Maria
AU  - Moreno-Navarrete JM
AD  - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio 
      Biomedica de Girona, CIBEROBN (CB06/03/010), and Instituto de Salud Carlos III, 
      Girona, Spain jmoreno@idibgi.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141230
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Adiponectin)
RN  - 0 (Adipoq protein, mouse)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (RNA, Messenger)
RN  - 0 (Slc2a4 protein, mouse)
RN  - 53-59-8 (NADP)
RN  - E1UOL152H7 (Iron)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 4.2.1.3 (Iron Regulatory Protein 1)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/cytology/metabolism
MH  - Adipogenesis/genetics/*physiology
MH  - Adiponectin/genetics
MH  - Adipose Tissue/*metabolism
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Cells, Cultured
MH  - Cytosol/metabolism
MH  - Diabetes Mellitus, Type 2/genetics/metabolism/pathology
MH  - Gene Expression
MH  - Gene Knockdown Techniques
MH  - Glucose Transporter Type 4/genetics
MH  - Humans
MH  - Iron/*metabolism
MH  - Iron Regulatory Protein 1/antagonists & inhibitors/genetics/*metabolism
MH  - Isocitrate Dehydrogenase/genetics
MH  - Mice
MH  - Middle Aged
MH  - NADP/metabolism
MH  - Obesity/genetics/metabolism/pathology
MH  - RNA, Messenger/genetics/metabolism
OTO - NOTNLM
OT  - NADPH
OT  - adipocyte differentiation
OT  - knockdown
EDAT- 2015/01/01 06:00
MHDA- 2015/06/24 06:00
CRDT- 2015/01/01 06:00
PHST- 2014/06/18 00:00 [received]
PHST- 2014/12/09 00:00 [accepted]
PHST- 2015/01/01 06:00 [entrez]
PHST- 2015/01/01 06:00 [pubmed]
PHST- 2015/06/24 06:00 [medline]
AID - fj.14-258996 [pii]
AID - 10.1096/fj.14-258996 [doi]
PST - ppublish
SO  - FASEB J. 2015 Apr;29(4):1529-39. doi: 10.1096/fj.14-258996. Epub 2014 Dec 30.