Palmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male mice

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dc.contributor.authorCheng, LCen_AU
dc.contributor.authorYu, YHen_AU
dc.contributor.authorSzabo, Aen_AU
dc.contributor.authorWu, YZen_AU
dc.contributor.authorWang, HQen_AU
dc.contributor.authorCamer, Den_AU
dc.contributor.authorHuang, XFen_AU
dc.date.accessioned2017-08-09T00:11:08Zen_AU
dc.date.available2017-08-09T00:11:08Zen_AU
dc.date.issued2015-05-01en_AU
dc.date.statistics2017-07-03en_AU
dc.description.abstractThe consumption of diets rich in saturated fat largely contributes to the development of obesity in modern societies. A diet high in saturated fats can induce inflammation and impair leptin signaling in the hypothalamus. However, the role of saturated fatty acids on hypothalamic leptin signaling, and hepatic glucose and lipid metabolism remains largely undiscovered. In this study, we investigated the effects of intracerebroventricular (icv) administration of a saturated fatty acid, palmitic acid (PA, C16:0), on central leptin sensitivity, hypothalamic leptin signaling, inflammatory molecules and hepatic energy metabolism in C57BL/6 J male mice. We found that the icv administration of PA led to central leptin resistance, evidenced by the inhibition of central leptin's suppression of food intake. Central leptin resistance was concomitant with impaired hypothalamic leptin signaling (JAK2-STAT3, PKB/Akt-FOXO1) and a pro-inflammatory response (TNF-α, IL1-β, IL-6 and pIκBa) in the mediobasal hypothalamus and paraventricular hypothalamic nuclei. Furthermore, the pre-administration of icv PA blunted the effect of leptin-induced decreases in mRNA expression related to gluconeogenesis (G6Pase and PEPCK), glucose transportation (GLUT2) and lipogenesis (FAS and SCD1) in the liver of mice. Therefore, elevated central PA concentrations can induce pro-inflammatory responses and leptin resistance, which are associated with disorders of energy homeostasis in the liver as a result of diet-induced obesity. © 2015, Elsevier Inc.en_AU
dc.identifier.citationCheng, L., Yu, Y., Szabo, A., Wu, Y., Wang, H., Camer, D., & Huang, X.-F. (2015). Palmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male mice. Journal of Nutritional Biochemistry, 26(5), 541-548. doi:10.1016/j.jnutbio.2014.12.011en_AU
dc.identifier.govdoc8383en_AU
dc.identifier.issn0955-2863en_AU
dc.identifier.issue5en_AU
dc.identifier.journaltitleJournal of Nutritional Biochemistryen_AU
dc.identifier.pagination541-548en_AU
dc.identifier.urihttp://dx.doi.org/10.1016/j.jnutbio.2014.12.011en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/8897en_AU
dc.identifier.volume26en_AU
dc.language.isoenen_AU
dc.publisherElsevieren_AU
dc.subjectHexadecanoic aciden_AU
dc.subjectLeptinen_AU
dc.subjectInflammationen_AU
dc.subjectGlucoseen_AU
dc.subjectLipidsen_AU
dc.subjectHypothalamusen_AU
dc.subjectMetabolismen_AU
dc.subjectMetabolic diseasesen_AU
dc.subjectCarboxylic acidsen_AU
dc.subjectLiveren_AU
dc.titlePalmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male miceen_AU
dc.typeJournal Articleen_AU
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