Cyclooxygenase-2 dependent metabolism of 20-hete increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes

Dong Hyun Kim, Nitin Puri, Komal Sodhi, J R Falck, Nader G. Abraham, Joseph Shapiro, Michal L. Schwartzman

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome P450 (CYP)-catalyzed-hydroxylation of arachidonic acid, induces oxidative stress and, in clinical studies, is associated with increased body mass index (BMI) and the metabolic syndrome. This study was designed to examine the effects of exogenous 20-HETE on mesenchymal stem cell (MSC)-derived adipocytes. The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases in humans) in MSCs decreased during adipocyte differentiation; however, exogenous administration of 20-HETE (0.1-1 M) increased adipogenesis in a dosedependent manner in these cells ( P > 0.05). The inability of a 20-HETE analog to reproduce these effects suggested the involvement of a metabolic product of 20-HETE in mediating its pro-adipogenic effects. A cyclooxygenase (COX)-1 selective inhibitor enhanced, whereas a COX-2 selective or a dual COX-1/2 inhibitor attenuated adipogenesis induced by 20-HETE. The COX-derived metabolite of 20-HETE, 20-OH-PGE 2 , enhanced adipogenesis and lipid accumulation in MSCs. The pro-adipogenic effects of 20-HETE and 20-OH-PGE 2 resulted in the increased expression of the adipogenic regulators PPAR and -catenin in MSC-derived adipocytes. Taken together we show for the fi rst time that 20-HETE-derived COX-2-dependent 20-OH-PGE 2 enhances mature infl amed adipocyte hypertrophy in MSC undergoing adipogenic differentiation.

Original languageEnglish (US)
Pages (from-to)786-793
Number of pages8
JournalJournal of Lipid Research
Volume54
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

Adiposity
Cyclooxygenase 2
Stem cells
Mesenchymal Stromal Cells
Adipocytes
Metabolism
Adipogenesis
Prostaglandins E
Cyclooxygenase 1
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Catenins
Hydroxylation
Peroxisome Proliferator-Activated Receptors
Oxidative stress
Cyclooxygenase 2 Inhibitors
Prostaglandin-Endoperoxide Synthases
Metabolites
Arachidonic Acid
Cytochrome P-450 Enzyme System
Hypertrophy

Keywords

  • Adipogenesis
  • Arachidonic acid
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Cyclooxygenase-2 dependent metabolism of 20-hete increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes. / Kim, Dong Hyun; Puri, Nitin; Sodhi, Komal; Falck, J R; Abraham, Nader G.; Shapiro, Joseph; Schwartzman, Michal L.

In: Journal of Lipid Research, Vol. 54, No. 3, 03.2013, p. 786-793.

Research output: Contribution to journalArticle

Kim, Dong Hyun ; Puri, Nitin ; Sodhi, Komal ; Falck, J R ; Abraham, Nader G. ; Shapiro, Joseph ; Schwartzman, Michal L. / Cyclooxygenase-2 dependent metabolism of 20-hete increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes. In: Journal of Lipid Research. 2013 ; Vol. 54, No. 3. pp. 786-793.
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AU - Puri, Nitin

AU - Sodhi, Komal

AU - Falck, J R

AU - Abraham, Nader G.

AU - Shapiro, Joseph

AU - Schwartzman, Michal L.

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AB - 20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome P450 (CYP)-catalyzed-hydroxylation of arachidonic acid, induces oxidative stress and, in clinical studies, is associated with increased body mass index (BMI) and the metabolic syndrome. This study was designed to examine the effects of exogenous 20-HETE on mesenchymal stem cell (MSC)-derived adipocytes. The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases in humans) in MSCs decreased during adipocyte differentiation; however, exogenous administration of 20-HETE (0.1-1 M) increased adipogenesis in a dosedependent manner in these cells ( P > 0.05). The inability of a 20-HETE analog to reproduce these effects suggested the involvement of a metabolic product of 20-HETE in mediating its pro-adipogenic effects. A cyclooxygenase (COX)-1 selective inhibitor enhanced, whereas a COX-2 selective or a dual COX-1/2 inhibitor attenuated adipogenesis induced by 20-HETE. The COX-derived metabolite of 20-HETE, 20-OH-PGE 2 , enhanced adipogenesis and lipid accumulation in MSCs. The pro-adipogenic effects of 20-HETE and 20-OH-PGE 2 resulted in the increased expression of the adipogenic regulators PPAR and -catenin in MSC-derived adipocytes. Taken together we show for the fi rst time that 20-HETE-derived COX-2-dependent 20-OH-PGE 2 enhances mature infl amed adipocyte hypertrophy in MSC undergoing adipogenic differentiation.

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