Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice

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dc.contributor.authorCheng, LCen_AU
dc.contributor.authorYu, YHen_AU
dc.contributor.authorZhang, QSen_AU
dc.contributor.authorSzabo, Aen_AU
dc.contributor.authorWang, HQen_AU
dc.contributor.authorHuang, XFen_AU
dc.date.accessioned2017-07-03T01:03:50Zen_AU
dc.date.available2017-07-03T01:03:50Zen_AU
dc.date.issued2015-09-05en_AU
dc.date.statistics2017-07-03en_AU
dc.description.abstractEpidemiological evidence suggests that the consumption of a diet high in n-6 polyunsaturated fatty acids (PUFA) is associated with the development of leptin resistance and obesity. We aim to examine the central effect of n-6 PUFA, arachidonic acid (ARA) on leptin sensitivity and leptin-regulated hepatic glucose and lipid metabolism. We found that intracerebroventricular injection of ARA (25 nmol/day) for 2.5 days reversed the effect of central leptin on hypothalamic JAK2, pSTAT3, pAkt, and pFOXO1 protein levels, which was concomitant with a pro-inflammatory response in the hypothalamus. ARA also attenuated the effect of central leptin on hepatic glucose and lipid metabolism by reversing the mRNA expression of the genes involved in gluconeogenesis (G6Pase, PEPCK), glucose transportation (GLUT2), lipogenesis (FAS, SCD1), and cholesterol synthesis (HMG-CoA reductase). These results indicate that an increased exposure to central n-6 PUFA induces central cellular leptin resistance with concomitant defective JAK2-STAT3 and PI3K-Akt signaling. © 2015, Elsevier Ireland Ltd.en_AU
dc.identifier.citationCheng, L., Yu, Y., Zhang, Q., Szabo, A., Wang, H., & Huang, X.-F. (2015). Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice. Molecular and Cellular Endocrinology, 412, 12-18. doi:10.1016/j.mce.2015.04.025en_AU
dc.identifier.govdoc8384en_AU
dc.identifier.issn0303-7207en_AU
dc.identifier.journaltitleMolecular and Cellular Endocrinologyen_AU
dc.identifier.pagination12-18en_AU
dc.identifier.urihttp://dx.doi.org/10.1016/j.mce.2015.04.025en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/8839en_AU
dc.identifier.volume412en_AU
dc.language.isoenen_AU
dc.publisherElsevieren_AU
dc.subjectLeptinen_AU
dc.subjectLipidsen_AU
dc.subjectArachidonic aciden_AU
dc.subjectHypothalamusen_AU
dc.subjectInflammationen_AU
dc.subjectMetabolismen_AU
dc.subjectDieten_AU
dc.subjectMiceen_AU
dc.titleArachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in miceen_AU
dc.typeJournal Articleen_AU
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