{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:03:52Z","timestamp":1792713832096,"version":"4.5.0"},"reference-count":37,"publisher":"Society for Neuroscience","issue":"42","license":[{"start":{"date-parts":[[2012,4,19]],"date-time":"2012-04-19T00:00:00Z","timestamp":1334793600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2011,10,19]]},"abstract":"<jats:p>The transcriptional coactivator PGC-1\u03b1 is a key regulator of cellular energy expenditure in peripheral tissues. Recent studies report that PGC-1\u03b1-null mice develop late-onset obesity and that the neuronal inactivation of PGC-1\u03b1 causes increased food intake. However, the exact role of PGC-1\u03b1 in the CNS remains unclear. Here we show that PGC-1\u03b1 directly regulates the expression of the hypothalamic neuropeptide oxytocin, a known central regulator of appetite. We developed a unique genetic approach in the zebrafish, allowing us to monitor and manipulate PGC-1\u03b1 activity in oxytocinergic neurons. We found that PGC-1\u03b1 is coexpressed with oxytocin in the zebrafish hypothalamus. Targeted knockdown of the zebrafish PGC-1\u03b1 gene activity caused a marked decrease in oxytocin mRNA levels and inhibited the expression of a transgenic GFP reporter driven by the oxytocin promoter. The effect of PGC-1\u03b1 loss of function on oxytocin gene activity was rescued by tissue-specific re-expression of either PGC-1\u03b1 or oxytocin precursor in zebrafish oxytocinergic neurons. PGC-1\u03b1 activated the oxytocin promoter in a heterologous cell culture system, and overexpression of PGC-1\u03b1 induced ectopic expression of oxytocin in muscles and neurons. Finally, PGC-1\u03b1 forms an<jats:italic>in vivo<\/jats:italic>complex with the oxytocin promoter in fed but not fasted animals. These findings demonstrate that PGC-1\u03b1 is both necessary and sufficient for the production of oxytocin, implicating hypothalamic PGC-1\u03b1 in the direct activation of a hypothalamic hormone known to control energy intake.<\/jats:p>","DOI":"10.1523\/jneurosci.1798-11.2011","type":"journal-article","created":{"date-parts":[[2011,10,19]],"date-time":"2011-10-19T21:18:14Z","timestamp":1319059094000},"page":"14835-14840","source":"Crossref","is-referenced-by-count":40,"title":["The Metabolic Regulator PGC-1\u03b1 Directly Controls the Expression of the Hypothalamic Neuropeptide 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