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. 2020 Dec;9(12):1168-1177.
doi: 10.1530/EC-20-0285.

Ghrelin in the lateral parabrachial nucleus influences the excitability of glucosensing neurons, increases food intake and body weight

Caishun Zhang  1 , Junhua Yuan  1 , Qian Lin  1 , Manwen Li  1 , Liuxin Wang  2 , Rui Wang  1 , Xi Chen  3 , Zhengyao Jiang  3 , Kun Zhu  4 , Xiaoli Chang  5 , Bin Wang  1   6 , Jing Dong  1   3
Affiliations

Ghrelin in the lateral parabrachial nucleus influences the excitability of glucosensing neurons, increases food intake and body weight

Caishun Zhang et al. Endocr Connect. 2020 Dec.

Abstract

Ghrelin plays a pivotal role in the regulation of food intake, body weight and energy metabolism. However, these effects of ghrelin in the lateral parabrachial nucleus (LPBN) are unexplored. C57BL/6J mice and GHSR-/- mice were implanted with cannula above the right LPBN and ghrelin was microinjected via the cannula to investigate effect of ghrelin in the LPBN. In vivo electrophysiological technique was used to record LPBN glucose-sensitive neurons to explore potential udnderlying mechanisms. Microinjection of ghrelin in LPBN significantly increased food intake in the first 3 h, while such effect was blocked by [D-Lys3]-GHRP-6 and abolished in GHSR-/- mice. LPBN ghrelin microinjection also significantly increased the firing rate of glucose-excited (GE) neurons and decreased the firing rate of glucose-inhibited (GI) neurons. Additionally, LPBN ghrelin microinjection also significantly increased c-fos expression. Chronic ghrelin administration in the LPBN resulted in significantly increased body weight gain. Meanwhile, no significant changes were observed in both mRNA and protein expression levels of UCP-1 in BAT. These results demonstrated that microinjection of ghrelin in LPBN could increase food intake through the interaction with growth hormone secretagogue receptor (GHSR) in C57BL/6J mice, and its chronic administration could also increase body weight gain. These effects might be associated with altered firing rate in the GE and GI neurons.

Keywords: energy metabolism; food intake; ghrelin; glucose-sensitive neurons; lateral parabrachial nucleus.

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Figures

Figure 1
Figure 1
Effects of ghrelin injection in LPBN on nocturnal feeding in mice. (A) Ghrelin increased food intake in 1, 2, 3 h after injection of ghrelin in LPBN. (B) [D-Lys3]-GHRP-6 blocked the effects of LPBN ghrelin on food intake in 2, 3 h after injection of ghrelin in LPBN. (C) Ghrelin receptor knockout abolished the effects of LPBN ghrelin on food intake in 1, 2, 3 h after injection of ghrelin in LPBN. *P < 0.05 ghrelin vs 0.9% NaCl, #P < 0.05 GHRP-6+ghrelin vs GHRP-6.
Figure 2
Figure 2
Effects of ghrelin injection in LPBN on long-time body weight gain in mice. After the injection of ghrelin, body weight gain was increased from the 4th day. *P < 0.05 ghrelin vs 0.9% NaCl.
Figure 3
Figure 3
Effects of ghrelin on LPBN glucose-sensitive neurons in vivo. (A) Ghrelin of LPBN affects the activity of glucose-excited neurons. (B) Ghrelin of LPBN affects the activity of glucose-inhibited neurons. The first arrow indicates the addition of 5 mM glucose, the second arrow indicates the 0.9% NaCl-treated control, and the third arrow indicates ghrelin (1.5 × 10−8 M) application. (a) Baseline before glucose application. (b) Firing rate after glucose application. (c) Firing rate recovered to baseline before 0.9% NaCl application. (d) Firing rate after 0.9% NaCl application and the baseline before ghrelin application. (e) Firing rate after ghrelin application.
Figure 4
Figure 4
Effects of long-term LPBN ghrelin on UCP-1 expression in BAT UCP-1 protein expression in BAT had no change in ghrelin group (n = 7) compared to 0.9% NaCl group (n = 6) (A), UCP-1 mRNA expression in BAT had no change in ghrelin group (n = 5) compared to 0.9% NaCl group (n = 4) (B) (P > 0.05).
Figure 5
Figure 5
Effects of LPBN ghrelin on c-fos expression in LPBN. Microinjection of ghrelin in LPBN increased c-fos expression in LPBN, ghrelin group (n = 3), 0.9% NaCl group (n = 3). *P < 0.05 ghrelin vs 0.9% NaCl. scp, superior cerebellar peduncle; MPBN, medial parabrachial nucleus.
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