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Am J Physiol Regul Integr Comp Physiol 284: R1454-R1465, 2003. First published January 30, 2003; doi:10.1152/ajpregu.00286.2002
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Vol. 284, Issue 6, R1454-R1465, June 2003

SPECIAL TOPICS
Peptides that Regulate Food Intake
Orexin gene expression is increased during states of hypertriglyceridemia

Katherine E. Wortley*, Guo-Qing Chang*, Zoya Davydova, and Sarah F. Leibowitz

The Rockefeller University, New York, New York 10021

Previous reports implicate the orexins in eating and body weight regulation. This study investigated possible functional relationships between hypothalamic orexins and circulating hormones or metabolites. In situ hybridization and quantitative PCR were used to examine orexin expression in the perifornical hypothalamus (PF) of rats and mice on diets varying in fat content and with differential propensity toward obesity. The results showed that orexin gene expression was stimulated by a high-fat diet in close association with elevated triglyceride levels, suggesting a functional relationship between these measures. Results obtained in obesity-prone rats and mice revealed a similar increase in orexin in close relation to triglycerides. A direct test of this orexin-triglyceride link was performed with Intralipid, which increased PF orexin expression along with circulating triglycerides. Whereas PF galanin is similarly stimulated by dietary fat, double-labeling immunofluorescence studies showed that orexin and galanin neurons are anatomically distinct. This evidence suggests that the orexins, like galanin, are "fat-responsive" peptides that respond to circulating lipids.

perifornical lateral hypothalamus; triglycerides; high-fat diet; obesity

* K. E. Wortley and G.-Q. Chang contributed equally to this work.




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