PMID- 24219292 OWN - NLM STAT- MEDLINE DCOM- 20140606 LR - 20220330 IS - 1208-6002 (Electronic) IS - 0829-8211 (Linking) VI - 91 IP - 6 DP - 2013 Dec TI - 15(S)-HETE-induced angiogenesis in adipose tissue is mediated through activation of PI3K/Akt/mTOR signaling pathway. PG - 498-505 LID - 10.1139/bcb-2013-0037 [doi] AB - 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. FAU - Soumya, Sasikumar J AU - Soumya SJ AD - a Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, Kerala 695 581, India. FAU - Binu, Sheela AU - Binu S FAU - Helen, Antony AU - Helen A FAU - Reddanna, Pallu AU - Reddanna P FAU - Sudhakaran, Perumana R AU - Sudhakaran PR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131017 PL - Canada TA - Biochem Cell Biol JT - Biochemistry and cell biology = Biochimie et biologie cellulaire JID - 8606068 RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (Hydroxyeicosatetraenoic Acids) RN - 0 (Morpholines) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, rat) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - 73945-47-8 (15-hydroxy-5,8,11,13-eicosatetraenoic acid) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adipose Tissue/blood supply/cytology/*drug effects/metabolism MH - Animals MH - Chromones/pharmacology MH - Endothelial Cells/cytology/*drug effects/metabolism MH - Enzyme Inhibitors/pharmacology MH - Epididymis/blood supply/cytology/*drug effects/metabolism MH - Gene Expression Regulation MH - Hydroxyeicosatetraenoic Acids/metabolism/*pharmacology MH - Male MH - Morpholines/pharmacology MH - Neovascularization, Pathologic MH - Phosphatidylinositol 3-Kinases/*genetics/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Platelet Endothelial Cell Adhesion Molecule-1/genetics/metabolism MH - Primary Cell Culture MH - Proto-Oncogene Proteins c-akt/*genetics/metabolism MH - Rats MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/*genetics/metabolism MH - Tissue Culture Techniques MH - Vascular Endothelial Growth Factor A/genetics/metabolism EDAT- 2013/11/14 06:00 MHDA- 2014/06/07 06:00 CRDT- 2013/11/14 06:00 PHST- 2013/11/14 06:00 [entrez] PHST- 2013/11/14 06:00 [pubmed] PHST- 2014/06/07 06:00 [medline] AID - 10.1139/bcb-2013-0037 [doi] PST - ppublish SO - Biochem Cell Biol. 2013 Dec;91(6):498-505. doi: 10.1139/bcb-2013-0037. Epub 2013 Oct 17.