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Role of cerebellar leptin signaling in motor-energy homeostasis

Role of cerebellar leptin signaling in motor-energy homeosta...

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2019中国生理学会学术年会暨张锡钧基金第十五届全国青...

作者：谢枢韬 Xiao-Yang ZHANG Wen-Xia WU Zi CHEN Jian-Jun WANG Jing-Ning ZHU State Key Laboratory of Pharmaceutical Biotechnology and Department of Physiology School of Life Sciencesand 2Institute for Brain SciencesNanjing University

Leptin is a hormone secreted by adipocytes and a critical signal that conveys peripheral metabolic information to brain for increasing energy expenditure, suppressing food intake and thereby regulating body weight and energy homeostasis.Most studies have focused on leptin signaling in the hypothalamic feeding centers.However, the expression of leptin receptors has also been detected in the cerebellum, a subcortical motor center involved not only in somatic motor control, but also in feeding behaviors and energy homeostasis.In the present study, we reveal that cerebellar nuclei（CN） neurons, the final outputs of the cerebellum, exhibit low spontaneous discharge rates and c-Fos expression in the HFD-induced or ZDF obese rats.The longest leptin receptor isoform Ob-Rb is selectively expressed in the glutamatergic projection neurons in the CN.The CN neurons show significant excitatory response to local leptin infusion in vivo.Moreover, microinjection of leptin into the CN and optogenetic/chemogenetic activation of CN glutamatergic neurons increase locomotor activities, but decrease food intake and reduce weight gain in ad libitum-fed as well as HFD-induced obese mice/rats.Consistently, knockdown of Ob-Rb, pharmacological blockage or chemogenetic inactivation of Ob-Rb in the CN decrease locomotor activities, whereas increase the daily food intake and elevates weight gain.These findings shed a light on the role of leptin receptor in the cerebellum, and suggest that the cerebellar leptin signaling on the glutamatergic projection neurons may play a critical role in motor control,body weight and motor-energy homeostasis.

关键词： Cerebellum cerebellar nucleus Leptin Locomotor activity Food intake Metabolism

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