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Article
Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice
Illawarra Health and Medical Research Institute
  • Licai Cheng, University of Wollongong
  • Yinghua Yu, University of Wollongong
  • Qingsheng Zhang, University of Wollongong
  • Alexander M Szabo, University of Wollongong
  • Hongqin Wang, University of Wollongong
  • Xu-Feng Huang, University of Wollongong
Publication Date
1-1-2015
RIS ID
100114
Publication Details

Cheng, L., Yu, Y., Zhang, Q., Szabo, A., Wang, H. & Huang, X. (2015). Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice. Molecular and Cellular Endocrinology, 412 12-18.

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.
Grant Number
NHMRC/573441
Citation Information
Licai Cheng, Yinghua Yu, Qingsheng Zhang, Alexander M Szabo, et al.. "Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice" (2015) p. 12 - 18
Available at: http://works.bepress.com/xhuang/156/