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Please use this identifier to cite or link to this item: http://apo.ansto.gov.au/dspace/handle/10238/8839

Title: Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice
Authors: Cheng, L
Yu, Y
Zhang, Q
Szabo, A
Wang, H
Huang, XF
Keywords: ARACHIDONIC ACID
LEPTIN
LIPIDS
ARACHIDONIC ACID
HYPOTHALAMUS
INFLAMMATION
Issue Date: 5-Sep-2015
Publisher: Elsevier
Citation: Cheng, 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: http://dx.doi.org/10.1016/j.mce.2015.04.025
Abstract: Epidemiological 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.
URI: http://dx.doi.org/10.1016/j.mce.2015.04.025
http://apo.ansto.gov.au/dspace/handle/10238/8839
ISSN: 0303-7207
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