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Pro-inflammatory cytokines in the paraventricular nucleus mediate the adipose afferent reflex in rats

  • Integrative physiology
  • Published:
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Abstract

Our previous study showed that the adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure. We also found that pro-inflammatory cytokines (PICs) in the hypothalamic paraventricular nucleus (PVN) potentiate the cardiac sympathetic afferent reflex in rats. However, the role of PICs in the PVN in regulating the AAR is still not clear. This study determined whether PICs in the PVN mediate the AAR in rats. The AAR was evaluated based on renal sympathetic nerve activity and mean arterial blood pressure in response to capsaicin injection into inguinal WAT (iWAT). PIC levels were measured by ELISA. PVN microinjection with the PICs tumor necrosis factor (TNF)–α or interleukin (IL)-1β enhanced the AAR in a dose-dependent manner. Furthermore, pretreatment via the bilateral microinjection of the TNF-α-blocker etanercept or IL-1β blocker IL-1ra into the PVN attenuated the AAR. In rats pretreated with TNF-α or IL-1β, a sub-response dose of angiotensin II (Ang II) significantly enhanced the AAR. Moreover, delivery of the angiotensin II type 1(AT1) receptor antagonist losartan into the PVN attenuated the effects of TNF-α or IL-1β on the AAR. In addition, stimulating either iWAT or retroperitoneal WAT with capsaicin increased TNF-α or IL-1β levels in the PVN, but the injection of capsaicin into the jugular vein, skeletal muscle, and skin had no effects on TNF-α or IL-1β levels in the PVN. These results suggest that TNF-α or IL-1β and Ang II in the PVN synergistically enhance the AAR in rats.

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Acknowledgments

The authors would like to thank Professor Guo-qing Zhu, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, for his technical assistance, and Peng Li and Wei-wei Chen for their help with experiments. We would also like to thank Editage (www.editage.cn) for English language editing.

Funding

This project was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81200186, 81670398, and 91639102), Shan-dong Provincial Natural Science Foundation, China (Grant No. ZR2018MC011), Yantai key research and development project (Grant No. 2017WS121), and the funding of Taishan Scholars of Shan-dong Province to Binzhou Medical University.

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Author notes

  1. Peng Lu and Li-wen Liang contributed equally to this work.

Authors and Affiliations

  1. Sino-US Translational Medicine Institute and College of Pharmacy, Binzhou Medical University, Yantai, 264003, China

    Peng Lu, Li-wen Liang, Ye-ying Sun & Zhen Shi

  2. Department of Cardiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264003, China

    Peng Lu

  3. Department of Physiology, Binzhou Medical University, 346 Guanhai Rd, Laishan District, Yantai, 264003, Shandong Province, China

    Li-wen Liang, Ai-li Xu, Shu-jun Jiang & Zhen Shi

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  1. Peng Lu
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Contributions

Zhen Shi conceived and designed the study; Peng Lu, Li-wen Liang, and Ai-li Xu performed experiments; Zhen Shi, Peng Lu, Li-wen Liang, and Ye-ying Sun analyzed data; Zhen Shi and Shu-jun Jiang wrote the paper; Peng Lu and Li-wen Liang contributed new methods.

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Correspondence to Zhen Shi.

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All animal work in this study was approved and performed in accordance with the Home Office UK Animals (Scientific Procedures) Act 1986 under the regulations and policies laid out by the Medical Ethics Committee of Binzhou Medical University.

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Lu, P., Liang, Lw., Xu, Al. et al. Pro-inflammatory cytokines in the paraventricular nucleus mediate the adipose afferent reflex in rats. Pflugers Arch - Eur J Physiol 472, 343–354 (2020). https://doi.org/10.1007/s00424-020-02356-7

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