Heme induced oxidative stress attenuates sirtuin1 and enhances adipogenesis in mesenchymal stem cells and mouse pre-adipocytes
Authors: Dong Hyun Kim
Michael Haarstad
Gaia Favero
Nader G Abraham
Nitin Puri
Steven Bohinc
Komal Sodhi
Eleonora Foglio
Journal: Journal of Cellular Biochemistry (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Oxidative stress; Heme; Adipogenesis; Adipocytes; Sirtuin 1
Affiliations: Department of Physiology and Pharmacology, College of Medicine, The University of Toledo, Toledo, Ohio 43614, USA.

Abstract:  Patho-physiological conditions with high oxidative stress, such as conditions associated with increased denatured heme-proteins, are associated with enhanced adipogenic response. This effect predominantly manifests as adipocyte hypertrophy characterized by dysfunctional, pro-inflammatory adipocytes exhibiting reduced expression of anti-inflammatory hormone, adiponectin. To understand how increased levels of cellular heme, a pro-oxidant molecule, modulates adipogenesis; the following study was designed to evaluate effects of heme on adipogenesis in human mesenchymal stem cells (hMSCs) and mouse pre-adipocytes (3T3L1). Experiments were conducted in the absence and in the presence of a superoxide dismutase (SOD) mimetic (tempol, 100 ¬µM). Heme (10 ¬µM) increased (P&lt;0.05) adipogenesis in hMSCs and mouse pre-adipocytes, where tempol alone (100 ¬µmol/L) attenuated adipogenesis in these cells (P&lt;0.05). Tempol also reversed heme-induced increase in adipogenesis in both hMSCs and mouse pre-adipocytes (P&lt;0.05). In addition, heme exposed 3T3L1 exhibited reduced (P&lt;0.05) expression of transcriptional regulator-sirtuin 1 (Sirt1), along with, increased (P&lt;0.05) expression of adipogenic markers peroxisome proliferators-activated receptor-gamma (PPARŒ≥), C/EBPŒ±, and aP2. These effects of heme were rescued (P&lt;0.05) in cells concurrently treated with heme and tempol (P&lt;0.05) and prevented in cells over-expressing Sirt1. Taken together, our results indicate that heme-induced oxidative stress inhibits Sirt1, thus un-inhibiting adipogenic regulators such as PPARŒ≥ and C/EBPŒ±; which in turn induce increased adipogenesis along with adipocyte hypertrophy in pre-adipocytes. Anti-oxidant induced offsetting of these effects of heme supports the role of heme-dependent oxidative stress in mediating such events. 

Retracted: No

PubPeer comments:
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 Retracted [19 July 2021] . ---------------------------------------------- The above article, published online on 26 June 2018 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid. ,