Novel leptin-regulated genes revealed by transcriptional profiling of the hypothalamic paraventricular nucleus

Tung, Yi-Chun Loraine, Ma, Marcella, Piper, Sarah, Coll, Anthony, O'Rahilly, Stephen and Yeo, Giles S. H. (2008) Novel leptin-regulated genes revealed by transcriptional profiling of the hypothalamic paraventricular nucleus. Journal of Neuroscience, 28 47: 12419-12426. doi:10.1523/JNEUROSCI.3412-08.2008

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Author Tung, Yi-Chun Loraine
Ma, Marcella
Piper, Sarah
Coll, Anthony
O'Rahilly, Stephen
Yeo, Giles S. H.
Title Novel leptin-regulated genes revealed by transcriptional profiling of the hypothalamic paraventricular nucleus
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2008-11-01
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.3412-08.2008
Open Access Status File (Publisher version)
Volume 28
Issue 47
Start page 12419
End page 12426
Total pages 8
Place of publication Washington, DC, United States
Publisher Society for Neuroscience
Formatted abstract
Leptin plays a major role in coordinating the integrated response of the CNS to changes in nutritional state. Neurons within the paraventricular nucleus (PVN) of the hypothalamus express leptin receptors and receive dense innervation from leptin receptor-expressing neurons in the arcuate nucleus. To obtain new insights into the effects of circulating leptin on PVN function, we compared global transcriptional profiles of laser-captured PVN from ad libitum fed mice versus 48 h fasted mice receiving either sham or leptin treatment intraperitoneally. Five hundred twenty-seven PVN-expressed genes were altered by fasting in a manner that was at least partially reversible by leptin. Consistent with previous reports, thyrotrophin releasing hormone mRNA levels were decreased by fasting but restored to fed levels with leptin treatment. mRNA levels of oxytocin, vasopressin, and somatostatin were also reduced by fasting and restored by leptin. Given the known effects of leptin on synaptic remodeling, it is notable that, among the top 15 genes that were positively regulated by leptin, five have been implicated in synaptic function and/or plasticity (basigin, apolipoprotein E, Gap43, GABAA receptor-associated protein, and synuclein-γ). Pathway analysis identified oxidative phosphorylation, in particular, genes encoding complex 1 proteins that play a role in ubiquinone biosynthesis, to be the predominant gene set that was significantly regulated in a leptin-dependent manner. Thus, in addition to its effects on the expression of a broad range of neuropeptides, leptin may also exert more general influences on synaptic function in, and the bioenergetic state of, the PVN.
Keyword Fasting
Laser-captured microdissection
Paraventricular nucleus
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Created: Wed, 19 Apr 2017, 15:49:06 EST by Sarah Piper on behalf of Learning and Research Services (UQ Library)