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Submitted on November 21, 2003
Accepted on April 22, 2004
Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, N. Y. 10021
* To whom correspondence should be addressed. E-mail: leibow{at}rockefeller.edu.
Little is known about the impact of circulating lipids on brain processes. Building on evidence that chronic fat consumption stimulates hypothalamic peptides in close association with elevated triglycerides (TG), this study examined whether an acute rise in TG levels, induced by a fat emulsion, can affect these hypothalamic systems. In normal-weight rats, intraperitoneal injection of Intralipid (20%, 5ml) during the first 4 h after injection produced a robust increase in TG levels and non-esterified fatty acids, while having no impact on glucose, insulin or leptin levels. This was accompanied by a marked increase in expression of particular orexigenic peptides, galanin, orexins and the opioid, enkephalin, known to be positively related to fat ingestion. This effect, similarly induced by 4 h of high-fat diet consumption, was detected in the paraventricular nucleus (PVN) for galanin, perifornical hypothalamus (PFH) for orexins, and PVN, PFH as well as arcuate nucleus (ARC) for enkephalin. It was not seen, however, for neuropeptide Y and agouti-related protein localized in the ARC, which are unaffected or reduced by dietary fat. This site-specificity was confirmed by c-Fos immunostaining, a marker of neuronal activity, which was increased by Intralipid in the PVN and PFH but not the ARC and was detected in 20% of orexin-expressing neurons in the PFH. These findings suggest that circulating lipids through different mechanisms may stimulate hypothalamic neurons, which synthesize specific feeding-stimulatory peptides that possibly contribute to hyperphagia on a fat-rich diet.
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