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Endothelial cell surface expressed chemotaxis and apoptosis regulator controls white adipose tissue lipolysis through modulation of PI3/AKT pathway (1095.8)
Author(s) -
Kilari Sreenivasulu,
Remadevi Indulekha,
Sahoo Daisy,
Ramchandran Ramani,
Wilkinson George
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1095.8
Subject(s) - medicine , endocrinology , protein kinase b , white adipose tissue , adipocyte , adipose tissue , biology , angiogenesis , lipolysis , phosphorylation , pten , chemistry , microbiology and biotechnology , signal transduction , pi3k/akt/mtor pathway
Endothelial cell specific chemotaxis receptor (ECSCR), a cell surface glycoprotein is thought be specifically expressed in Endothelial cells (EC). ECSCR is involved in EC migration, apoptosis and proliferation (Verma et al., 2010). Our previous results indicate that VEGF stimulation induces ECSCR and VEGFR2 complex formation, while loss of ECSCR reduced VEGF induced VEGFR2 activation and impaired AKT and ERK phosphorylation (Kilari et al., 2013). Here, we demonstrate that ECSCR protein is highly expressed in white adipose tissues (WAT) and lungs of mice. Immunohistochemistry of mouse tissue sections reveal ECSCR protein in blood vessels of lung and skeletal muscles, and in precursors and mature white adipocytes. Furthermore, ECSCR protein increases with progression of adipocyte differentiation in 3T3L1 cell pre‐adipocyte model, suggesting that ECSCR contributes to adipocyte maturation. Therefore, we investigated the function of ECSCR in WAT and mice physiology using our ECSCR knockout model. Our results indicate that homozygous ECSCR null mouse are viable and fertile with elevated circulatory triglycerides and increased triglyceride partition into VLDL and free fatty acids without changes in total cholesterol. These results suggest increased lipolysis in ECSCR null mice. Interestingly, histology of WAT of ECSCR null mice shows fewer fully inflated “signet” adipocyte profiles, but no overt adipose pathology. In line with these results, WAT of ECSCR null mice show reduced AKT phosphorylation without changes in total AKT levels. Moreover, we demonstrate direct association of ECSCR and PTEN, a lipid phosphatase suppressor of AKT activation, which dephosphorylates PIP3, suggesting that loss of ECSCR directly modulates the AKT pathway. Taken together, these results indicate that ECSCR regulates adipose tissue lipolysis, via modulating PI3K/AKT pathway. Future studies will examine control of lipolysis in ECSCR deficient cells following adrenergic or insulin stimulation.