https://scholars.lib.ntu.edu.tw/handle/123456789/563770
標題: | Hyperglycemia enhances adipogenic induction of lipid accumulation: Involvement of extracellular signal-regulated protein kinase 1/2, phosphoinositide 3-kinase/Akt, and peroxisome proliferator-activated receptor γ signaling | 作者: | Chia C.C. RONG-SEN YANG KEH-SUNG TSAI Feng M.H. Liu S.H. |
公開日期: | 2007 | 卷: | 148 | 期: | 9 | 起(迄)頁: | 4267-4275 | 來源出版物: | Endocrinology | 摘要: | The molecular events of hyperglycemia-triggered increase in adipogenic induction of lipid accumulation remain unclear. We examined the effects of hyperglycemia on adipogenic induction of lipid accumulation and its involved signaling molecules, such as phosphoinositide 3-kinase (PI3K), ERKs, and peroxisome proliferator-activated receptor γ (PPARγ). Bone marrow-derived mesenchymal stem cells (MSCs) isolated from FVB/N mice were capable of differentiating into adipocytes in adipogenic medium. The effects of high glucose (HG) (25.5 mM) were assessed in vitro by RT-PCR, ELISA, flow cytometry, immunostaining, and immunoblotting. The in vivo effect of hyperglycemia was further studied in streptozotocin (STZ)-induced diabetic FVB/N mice. Exposure of MSCs to HG enhanced adipogenic induction of lipid accumulation as compared with 5.5 mM glucose. HG increased PPARγ expression and PI3K activity and its downstream effector Akt phosphorylation during adipogenesis. Inhibition of PI3K/Akt activity with PI3K inhibitor LY294002 or by expressing the dominant negative p85 or Akt prevented the HG-enhanced PPARγ-dependent adipogenic induction of lipid accumulation. Moreover, HG increased the phosphorylation of ERK1/2 during adipogenesis. MAPK/ERK inhibitor PD98059 inhibited the PI3K activity, Akt phosphorylation, and lipid accumulation triggered by HG. PI3K inhibitor LY294002 did not affect the HG-increased ERK1/2 phosphorylation during adipogenesis. We next observed that adipogenic induction of lipid accumulation of MSCs isolated from STZ-induced diabetic mice is enhanced. Moreover, triglyceride, PPARγ expression, phosphorylated Akt and ERK1/2, and marrow fat in bones of STZ-diabetic mice were also increased. These results suggest that hyperglycemia enhances the adipogenic induction of lipid accumulation through an ERK1/2-activated PI3K/Akt-regulated PPARγ pathway. Copyright ? 2007 by The Endocrine Society. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-34548103553&doi=10.1210%2fen.2007-0179&partnerID=40&md5=85a51c548f1682a66fe1ec30201c5b88 https://scholars.lib.ntu.edu.tw/handle/123456789/563770 |
ISSN: | 0013-7227 | DOI: | 10.1210/en.2007-0179 | SDG/關鍵字: | 2 (2 amino 3 methoxyphenyl)chromone; 2 morpholino 8 phenylchromone; fat; glucose; lipid; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase inhibitor; peroxisome proliferator activated receptor gamma; phosphatidylinositol 3 kinase; protein kinase B; protein p85; streptozocin; triacylglycerol; adipocyte; adipogenesis; animal cell; animal experiment; animal model; animal tissue; article; bone marrow; cell differentiation; cell isolation; comparative study; enzyme activity; enzyme inhibition; enzyme linked immunosorbent assay; enzyme phosphorylation; exposure; flow cytometry; hyperglycemia; immunoblotting; immunohistochemistry; in vitro study; in vivo study; lipid storage; male; mesenchymal stem cell; molecule; mouse; nonhuman; priority journal; protein expression; reverse transcription polymerase chain reaction; streptozocin diabetes; 1-Phosphatidylinositol 3-Kinase; Adipogenesis; Animals; Cell Culture Techniques; Diabetes Mellitus, Experimental; Flow Cytometry; Hyperglycemia; Lipids; Male; Mesenchymal Stem Cells; Mice; Phosphorylation; PPAR gamma; Protein Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction |
顯示於: | 醫學系 |
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