Cristin-resultat-ID: 1593672
Sist endret: 19. februar 2019, 12:25
NVI-rapporteringsår: 2018
Resultat
Vitenskapelig artikkel
2018

Synthesis and biological evaluations of marine oxohexadecenoic acids: PPARα/γ dual agonism and anti-diabetic target gene effects

Bidragsytere:
  • Thomas Sæther
  • Steinar M Paulsen
  • Jørn Eivind Tungen
  • Anders Vik
  • Marius Aursnes
  • Torgeir Holen
  • mfl.

Tidsskrift

European Journal of Medicinal Chemistry
ISSN 0223-5234
e-ISSN 1768-3254
NVI-nivå 1

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2018
Publisert online: 2018
Trykket: 2018
Volum: 155
Sider: 736 - 753
Open Access

Importkilder

Scopus-ID: 2-s2.0-85048888909

Beskrivelse Beskrivelse

Tittel

Synthesis and biological evaluations of marine oxohexadecenoic acids: PPARα/γ dual agonism and anti-diabetic target gene effects

Sammendrag

Obesity and associated disorders such as metabolic syndrome and type 2 diabetes (T2D) have reached epidemic proportions. Several natural products have been reported as Peroxisome Proliferator-Activated Receptor (PPAR) agonists, functioning as lead compounds towards developing new anti-diabetic drugs due to adverse side effects of existing PPAR drugs. We recently isolated and identified (7E)-9-oxohexadec-7-enoic acid (1) and (10E)-9-oxohexadec-10-enoic acid (2) from the marine algae Chaetoceros karianus. Herein we report the total synthesis, pharmacological characterization, and biological evaluations of these naturally occurring oxo-fatty acids (oFAs). The syntheses of 1 and 2 afforded sufficient material for extensive biological evaluations. Both oFAs show an appreciable dose-dependent activation of PPARα and -γ, with EC50 values in the micromolar range, and an ability to regulate important PPAR target genes in hepatocytes and adipocytes. Moreover, both 1 and 2 are able to drive adipogenesis when evaluated in the Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocyte cell model, but with lowered expression of adipocyte markers and reduced lipid accumulation compared to the drug rosiglitazone. This seems to be caused by a transient upregulation of PPARγ and C/EBPα expression. Importantly, whole transcriptome analysis shows that both compounds induce anti-diabetic gene programs in adipocytes by upregulating insulin-sensitizing adipokines and repressing pro-inflammatory cytokines.

Bidragsytere

Aktiv cristin-person

Thomas Sæther

  • Tilknyttet:
    Forfatter
    ved Kjernereseptorgruppa ved Universitetet i Oslo
Aktiv cristin-person

Steinar Martin Paulsen

Bidragsyterens navn vises på dette resultatet som Steinar M Paulsen
  • Tilknyttet:
    Forfatter
    ved Kardiovaskulær forskningsgruppe ved UiT Norges arktiske universitet

Jørn Eivind Tungen

  • Tilknyttet:
    Forfatter
    ved Seksjon for farmasøytisk kjemi ved Universitetet i Oslo

Anders Vik

  • Tilknyttet:
    Forfatter
    ved Seksjon for farmasøytisk kjemi ved Universitetet i Oslo

Marius Aursnes

  • Tilknyttet:
    Forfatter
    ved Seksjon for farmasøytisk kjemi ved Universitetet i Oslo
1 - 5 av 8 | Neste | Siste »