15(S)-HETE-induced angiogenesis in adipose tissue is mediated through activation of PI3K/Akt/mTOR signaling pathway.
Chronic low-grade inflammation underlies obesity and associated metabolic dysfunctions. Lipoxygenase pathways are activated in adipose tissue during obese conditions. Since adipogenesis is associated with angiogenesis, the present study was designed to examine the role of 15-lipoxygenase metabolite, 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] on angiogenesis in adipose tissue. Results showed that 15(S)-HETE induced sprouting in fat pad stromovascular tissues, induced morphological changes relevant to angiogenesis in endothelial cells derived from adipose tissue, upregulated the production of CD31, upregulated the gene level expression and production of vascular endothelial growth factor (VEGF), indicating the pro-angiogenic effect of 15(S)-HETE. LY294002, an inhibitor of PI3K-Akt pathway, and rapamycin, inhibitor of mammalian target of rapamycin (mTOR), significantly reversed the effect of 15(S)-HETE. 15(S)-HETE also induced activation of Akt and mTOR. These observations suggest that 15(S)-HETE stimulates angiogenesis in adipose tissue through activation of PI3K/Akt/mTOR signaling.
a Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, Kerala 695 581, India.
Sasikumar J
SJ
Soumya
Sheela
S
Binu
Antony
A
Helen
Pallu
P
Reddanna
Perumana R
PR
Sudhakaran
D000273:Adipose Tissue / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004822:Epididymis / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D046509:Tissue Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D002867:Chromones; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C546845:mTOR protein, rat