Orexin receptor type 2  agonism inhibits thermogenesis in brown adipose tissue by attenuating afferent innervation

Mo-qiu Jia; Yong-jin Wang; Kang Fu; Han Jiao; Jia Sun; Yuanqing Gao

doi:10.7555/JBR.36.20220033

Volume 36 Issue 3

May 2022

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The Journal of Biomedical Research > 2022 > 36(3): 195-207. > DOI: 10.7555/JBR.36.20220033

Mo-qiu Jia, Yong-jin Wang, Kang Fu, Han Jiao, Jia Sun, Yuanqing Gao. Orexin receptor type 2 agonism inhibits thermogenesis in brown adipose tissue by attenuating afferent innervation[J]. The Journal of Biomedical Research, 2022, 36(3): 195-207. DOI: 10.7555/JBR.36.20220033

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Orexin receptor type 2 agonism inhibits thermogenesis in brown adipose tissue by attenuating afferent innervation

Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, China

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Corresponding author:
Yuanqing Gao, Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu 211166, China. Tel: +86-25 86868467. E-mail: yuanqinggao@njmu.edu.cn
Received Date: February 13, 2022
Revised Date: March 31, 2022
Accepted Date: April 10, 2022
Available Online: May 27, 2022

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Abstract

Abstract

Orexin signaling has been associated with energy expenditure and brown adipose tissue (BAT) function. However, conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis. In this study, we show that a specific orexin receptor type 2 (OX2R) agonist [Ala11, D-Leu15]-OxB (OB-Ala) inhibited intrascapular brown adipose tissue (iBAT) thermogenesis by reducing sympathetic output to iBAT. This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself. Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus. Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop. Our study uncovers a novel primary action site of orexin in the regulation of energy balance.
- orexin receptor type 2,
- brown adipose tissue,
- thermogenesis

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References

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