Session: OR15-Adipokine Action
Room 303 (Moscone Center)
Notch and FoxO1 coordinate metabolism and differentiation in a variety of cell types, and genetic/pharmacologic blockade of Notch signaling increases insulin sensitivity (2). FoxO1 gain-of-function blocks differentiation of both adipocyte and myocyte cell lines, which can be rescued by inhibition of Notch in myocytes (3, 4). Notch1 regulates expression of adipogenic transcription factors in vitro, and down-regulation of Notch1 prevents adipocyte differentiation (5). Confusingly, Notch activation by Jagged1, or constitutive expression of Notch target Hes1, prevents differentiation of 3T3-L1 preadipoctyes (6). No study as yet has addressed the potential role of Notch signaling in adipocyte-type specification, or the presence and regulation of Notch signaling in vivo.
Using qRT-PCR, we examined transcription of components of the Notch cascade in BAT, SCAT and VAT in control v. cold-exposed mice, a model of brown adipogenesis. We show that Notch target Hes1 is repressed by 50% in VAT but induced 5.5-fold in BAT following cold exposure (n=6/condition, p<0.05). Notch receptors and ligands are also variably regulated in response to cold exposure (p<0.05). Notch target expression in VAT also appears to be affected in multiple metabolic conditions.
These data indicate that Notch signaling is active in vivo and is regulated in an adipose-depot specific manner, possibly participating in adipocyte lineage. To investigate in greater detail, we have developed mice with adipose-specific knockout of components of Notch signaling, and will present data that further characterize the role of Notch in adipogenesis.
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