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Nocturnin, an Induciable Deadenylase, Promotes the Adipogenesis and Lipolysis of White Adipose Tissue

Gilbert, Misty Rae
Format
Thesis/Dissertation; Online
Author
Gilbert, Misty Rae
Advisor
Green, Carla
Menaker, Mike
Kozminski, Keith
Provencio, Ignacio
Abstract
Circadian clocks, present in a variety of tissues, respond and entrain to environmental stimuli via the acute regulation of gene expression. Nocturnin, a rhythmically expressed deadenylase, was found to be an immediate early gene inducible in vitro by two stimuli that activate a wide range of signaling pathways, serum and the phorbol ester TPA. In this dissertation, I report the acute induction of Nocturnin to two specific stimuli, one of which is demonstrated in vivo, in adipose tissue. Nocturnin expression is acutely induced by insulin in 3T3-L1 pre-adipocytes, and siRNA-mediated knockdown of Nocturnin results in decreased adipogenic marker expression indicating a role for Nocturnin in promoting adipogenesis. I also report that Nocturnin expression in liver and in white adipose tissue is not dependent upon or induced by feeding. Nocturnin expression is not rhythmic in the white adipose tissue of ad libitum fed mice. However Nocturnin's expression becomes rhythmic in the white adipose tissue of restricted fed mice. Furthermore, suggesting that Nocturnin's rhythmicity in white adipose tissue under this feeding paradigm is due to an acute induction, Nocturnin expression is induced by fasting in restricted fed mice. I also demonstrate that Nocturnin is acutely induced in 3T3-L1 adipocytes by the beta-adrenergic receptor agonist isoproterenol and by a forskolin-induced rise in cAMP levels, two events which occur during hormone-induced lipolysis, suggesting that Nocturnin may mediate lipolysis in white adipose tissue. Further study of Nocturnin's role in the development and function of white adipose tissue will advance our knowledge regarding the links between circadian clocks and metabolism and the rapid redirection of cellular resources in response to extracellular stimuli. Note: Abstract extracted from PDF text
Language
English
Published
University of Virginia, Department of Biology, PHD, 2010
Published Date
2010-05-01
Degree
PHD
Collection
Libra ETD Repository
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