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E4 orf‐1 gene of adipogenic human adenovirus Ad‐36 enhances cAMP and insulin signaling pathways and induces differentiation in preadipocytes
Author(s) -
Rogers Pamela,
Fusinski Keith,
Loiler Scott,
Rathod Miloni,
Holland Thomas C,
Dhurandhar Nikhil V
Publication year - 2006
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.20.4.a165
Subject(s) - adipogenesis , signal transduction , biology , cellular differentiation , insulin , insulin receptor , microbiology and biotechnology , endocrinology , 3t3 l1 , medicine , chemistry , insulin resistance , adipose tissue , gene , biochemistry
Human adenovirus Ad‐36 increases adiposity in experimentally infected animals and shows association with human obesity. Ad‐36 induces greater differentiation of human primary preadipocytes and rodent preadipocytes (3T3‐L1 cells), even in the absence of differentiation inducers ‐ methyl isobutyl xanthine, dexamethasone and insulin (MDI). The lipogenic effect of Ad‐36 on preadipocytes may contribute to its in‐vivo adipogenic effect. We investigated cellular pathways of preadipocyte differentiation modulated by Ad‐36 and candidate viral genes. MDI induces preadipocyte differentiation by activating cAMP and insulin signaling pathways. Consistent with fact that Ad‐36 causes preadipocyte differentiation even without MDI, Ad‐36 infected 3T3‐L1 cells showed enhanced activation of insulin signaling pathway. To identify the contribution of Ad‐36 genes to the effect, 3T3‐L1 cells stably expressing Ad‐36 E1A, E4orf‐1 genes or the null vector were prepared. E4 orf‐1 expressing cells increased spontaneous differentiation, and enhanced cAMP and insulin signaling pathways as determined by elevated cAMP levels, cAMP response element binding protein activity and PI3 Kinase activity. The role of E4orf‐1 in differentiation was further confirmed by attenuating its expression in Ad‐36 infected 3T3‐L1 cells by RNAi technique, which significantly reduced lipid accumulation. These data show that E4 orf‐1 enhances cAMP and insulin signaling pathways and induces differentiation in preadipocytes.