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Review
. 2012 Jan;97(1-2):1-16.
doi: 10.1016/j.prostaglandins.2011.10.002. Epub 2011 Nov 15.

Epoxyeicosatrienoic acids and heme oxygenase-1 interaction attenuates diabetes and metabolic syndrome complications

Angela Burgess  1 , Luca Vanella, Lars Bellner, Michal L Schwartzman, Nader G Abraham
Affiliations
Review

Epoxyeicosatrienoic acids and heme oxygenase-1 interaction attenuates diabetes and metabolic syndrome complications

Angela Burgess et al. Prostaglandins Other Lipid Mediat. 2012 Jan.

Abstract

MSCs are considered to be the natural precursors to adipocyte development through the process of adipogenesis. A link has been established between decreased protective effects of EETs or HO-1 and their interaction in metabolic syndrome. Decreases in HO-1 or EET were associated with an increase in adipocyte stem cell differentiation and increased levels of inflammatory cytokines. EET agonist (AKR-I-27-28) inhibited MSC-derived adipocytes and decreased the levels of inflammatory cytokines. We further describe the role of CYP-epoxygenase expression, HO expression, and circulating cytokine levels in an obese mouse, ob/ob(-/-) mouse model. Ex vivo measurements of EET expression within MSCs derived from ob/ob(-/-) showed decreased levels of EETs that were increased by HO induction. This review demonstrates that suppression of HO and EET systems exist in MSCs prior to the development of adipocyte dysfunction. Further, adipocyte dysfunction can be ameliorated by induction of HO-1 and CYP-epoxygenase, i.e. EET.

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Figures

Figure 1
Figure 1
A schematic diagram of conditioning of MSCs by microenvironmental niches. Differentiation potential is based on the position of a given cell within the colony. Clonally derived MSCs behave differently in response to soluble factors because of microenvironmental preconditioning.
Figure 2
Figure 2
Enzyme intermediates of heme biosynthetic and degradative pathways. Modified from [20, 21, 156].
Figure 3
Figure 3
Schematic representation of the heme degradative pathway.
Figure 4
Figure 4
The three metabolic pathways of arachidonic acid (AA). HETE, hydroxyeicosatetraenoic acid; EET, epoxyeicosatrienoic acid.
Figure 5
Figure 5
Schematic diagram of epoxyeicosatrenoic acid synthesis from arachidonic acid and conversion into corresponding diols by epoxide hydrolase.
Figure 6
Figure 6
Molecular mechanisms underlying adipocyte dysfunction in a hypertrophied adipocyte. Hyperglycemia results in the increase of ROS production within the mitochondria via a number of mechanisms including a reduction in the glutathione/glutathione disulfide ratio. Overloading the endoplasmic reticulum (ER) with FFA results in impaired protein folding and an unfolded protein response (UPR). UPR results in an increase of reduced molecular oxygen which acts as cellular toxic ROS. ROS generation mediates a pro-inflammatory cascade resulting in insulin resistance.
Figure 7
Figure 7
The effect of HO-1 and HO-2 siRNA on adipogenesis. Lipid droplets area was determined by Oil red O staining after 14 days. * p<0.01 vs. control and #p<0.001 vs. HO-1 siRNA. Each bar represents means ± SE of 5 independent experiments. SnMP, inhibitor of HO activity was used as a control.
Figure 8
Figure 8
Overview of stages of adipocyte differentiation. PPAR-y, peroxisome proliferator-activated receptor-y; C/EBP,CCAAT/enhancer binding protein).
Figure 9
Figure 9
Dose response effect of EET agonist AKR-I-27-28 on HO-2𢈒/− derived MSC adipocyte differentiation. EET agonist AKR-I-27-28 attenuates adipocyte differentiation in a dose dependent manner.
FIG 10
FIG 10
HO-1 and EET effects on adipogenesis and adipose tissue.
See this image and copyright information in PMC

References

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