QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 19, 2008, 28(47):12419-12426; doi:10.1523/JNEUROSCI.3412-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tung, Y.-C. L. Articles by Yeo, G. S. H. PubMed PubMed Citation Articles by Tung, Y.-C. L. Articles by Yeo, G. S. H.

 Previous Article  |  Next Article 

Cellular/Molecular
Novel Leptin-Regulated Genes Revealed by Transcriptional Profiling of the Hypothalamic Paraventricular Nucleus

Yi-Chun Loraine Tung, Marcella Ma, Sarah Piper, Anthony Coll, Stephen O'Rahilly, and Giles S. H. Yeo

University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom

Correspondence should be addressed to Giles S. H. Yeo, University of Cambridge Metabolic Research Laboratories, Level 4, Institute of Metabolic Science, Box 289, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Email: gshy2{at}cam.ac.uk

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, GABA_A receptor-associated protein, and synuclein-). 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.

Key words: leptin; fasting; laser-captured microdissection; hypothalamus; paraventricular nucleus; microarray; gene

---

Received July 21, 2008; revised Oct. 4, 2008; accepted Oct. 6, 2008.

Correspondence should be addressed to Giles S. H. Yeo, University of Cambridge Metabolic Research Laboratories, Level 4, Institute of Metabolic Science, Box 289, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Email: gshy2{at}cam.ac.uk

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help