1. Calcitonin acts on agouti-related peptide neurons to regulate energy balance.
- Author
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Zhu Yangyang, Wang Jinghui, Xuan Ye, Chen Liwei, Zhang Yi, and Hu Cheng
- Abstract
Objective To investigate whether calcitonin can regulate energy balance via agouti-related peptide (AgRP) neurons. Methods The 12-week-old male C57BL/6 mice fed normal chow diet were divided into free-feeding group and 24-h fasting group, while 6-week-old male C57BL/6 mice were divided into normal chow diet group and high-fat diet group fed for 3 months, with three mice in each group, and the expression of calcitonin receptor (Calcr) in brain sections was detected by immunofluorescence staining. Twelve 6-week-old male C57BL/6 mice were fed with high-fat diet for 6 months to establish a high-fat diet-fed mouse model. After lateral ventricular cannulation, the mice were divided into saline lateral ventricular injection group (lateral ventricular injection of 1 µl saline) and salmon calcitonin (sCT) lateral ventricular injection group [lateral ventricular injection of 1 µl sCT (1 µg/µl)], with six mice in each group. Body weight and food intake were measured for 24 hours after injection. Oxygen consumption, carbon dioxide production and energy expenditure were measured after injection by Oxymax/CLAMS indirect calorimetry system. The 12-week-old normal chow diet-fed male C57BL/6 mice were divided into saline intraperitoneal injection group (intraperitoneal injection, 10 ml/kg) and sCT intraperitoneal injection group (intraperitoneal injection, 150 µg/kg), with three mice in each group, and the expression of AgRP, c-Fos, phosphorylated signal transducer and transcriptional activator 3 (pStat3) in brain sections was detected by immunofluorescence staining. Independent-samples t test was used for comparison between two groups. Results Compared with free-feeding group, Calcr expression in the arcuate nucleus was significantly decreased in 24-h fasting group (P<0.05); compared with normal chow diet group, Calcr expression in the hypothalamic arcuate nucleus was significantly decreased in high-fat diet group (P<0.05). Compared with saline lateral ventricular injection group, body weight and food intake were significantly reduced in sCT lateral ventricular injection group (P<0.05), while oxygen consumption, carbon dioxide production and energy expenditure were significantly increased in sCT lateral ventricular injection group (P<0.05). Compared with saline intraperitoneal injection group, double immunofluorescence staining of AgRP and c-Fos in the arcuate nucleus was significantly decreased, AgRP expression in the paraventricular nucleus was significantly decreased, and c-Fos expression in the paraventricular nucleus was significantly increased in sCT intraperitoneal injection group (P<0.05). Compared with saline intraperitoneal injection group, the expression of pStat3 in the arcuate nucleus was significantly increased in sCT intraperitoneal injection group (P<0.05). Conclusions Calcr in the arcuate nucleus is closely related to energy balance. Calcitonin can inhibit the expression of AgRP and the activity of AgRP neurons via Stat3 pathway, which in turn suppresses appetite and promotes energy expenditure. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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