Original Research ARTICLE
Leptin-mediated Sympatho-excitation in Obese Rats: Role for Neuron-Astrocyte Crosstalk in the Arcuate Nucleus
- 1University of South Dakota, United States
Introduction: Accumulated evidence indicates that enhanced sympathetic activation is associated with obesity. Hypothalamic leptin-mediated signaling may contribute to the exaggerated sympatho-excitation in obesity. The present study was conducted to investigate “neuron-astrocyte” interactions regulating leptin signaling within the arcuate nucleus (ARCN) of hypothalamus in obese rats.
Methods and Results: Obesity was induced by high-fat diet (HFD, 42% fat for 12 weeks) in Sprague Dawley rats. We found that leptin receptor was localized in both neurons and astrocytes in the ARCN. In the HFD obese rats, the expression of leptin receptor was increased in the ARCN compared to the normal diet rats. The HFD rats had increased level of glial fibrillary acidic protein (GFAP) in the ARCN. In anaesthetized condition, electrophysiological study showed that microinjections of leptin into the ARCN induced increases in renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in both control and HFD rats. Microinjection of leptin elicited significant higher increases in RSNA and MAP in the ARCN in the HFD rats. Pre-inhibition of astrocytes with astrocytic metabolic inhibitor fluorocitrate reduced leptin-induced RSNA, MAP and HR responses within the ARCN. Furthermore, we found that the expressions of astrocyte specific glutamate transporters, excitatory amino acid transporter 1 (EAAT1) and EAAT2 were decreased within the ARCN in the HFD rats. In cultured astrocytic C6 cells, the levels of GFAP, EAAT1 and EAAT2 were significantly changed in response to 24 hours leptin simulation.
Conclusion: The results suggested that leptin signaling might be via neuron-astrocyte interactions in the ARCN, contributing to the exaggerated sympatho-excitation observed in obese rats. The effects might be mediated by the action of leptin regulating astrocytic glutamate transporters within the ARCN of the hypothalamus.
Keywords: sympathetic nerve activity, Obesity, glial cells, Hypothalamus, Leptin, Blood Pressure, Autonomic Function
Received: 04 Jun 2019;
Accepted: 28 Oct 2019.
Copyright: © 2019 Liu and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mx. Hong Zheng, University of South Dakota, Vermillion, 57069-2390, South Dakota, United States, firstname.lastname@example.org