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

Gilbert, Misty Rae, Department of Biology, University of Virginia
Green, Carla, Department of Biology, University of Virginia
Provencio, Ignacio, Department of Biology, University of Virginia
Kozminski, Keith, Department of Biology, University of Virginia
Menaker, Mike, Department of Biology, University of Virginia

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.

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PHD (Doctor of Philosophy)
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