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Updated: Sep 14, 2025

Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration
Published on: March 17, 2014
UCP2 mediates mitochondrial dynamics to induce AgRP neuronal activity
Sungho Jin1, Nal Ae Yoon1, Zhong-Wu Liu2
1Institute of Human Nutrition, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Objectives:
The hypothalamic agouti-related protein (AgRP)- expressing neurons regulate feeding and whole-body energy homeostasis. A growing body of evidence indicates that changes in mitochondrial dynamics, such as fission and fusion, play a crucial role in regulating AgRP neuronal activity. However, the mechanisms underlying this process remain to be elucidated. Here, we showed a role of mitochondrial UCP2-mediated mitochondrial dynamics in AgRP neurons in regulating AgRP neuronal activity and fasting-induced feeding behavior.
Methods:
We analyzed mitochondrial morphology, expression of activated dynamin-related protein 1 (DRP1), and mRNA expression levels of uncoupling protein 2 (Ucp2) in AgRP neurons of mice that were either in fed or fasted states. We then generated a mouse model in which Ucp2 was selectively deleted from adult AgRP neurons to assess the role of this mitochondrial protein in feeding behavior and whole-body energy metabolism.
Results:
We show fasting-induced AgRP neuronal activation is associated with UCP2-mediated mitochondrial fission and mitochondrial fatty acid utilization in AgRP neurons. In line with this, mice lacking UCP2 in AgRP neurons (Ucp2AgRPKO) show attenuated fasting- or ghrelin-induced AgRP neuronal activation and feeding behaviors and exhibited a significant decrease in body weight and fat mass accompanied by a significant increase in energy expenditure.
Conclusions:
Altogether, our data revealed that UCP2-mediated mitochondrial dynamics and fatty acids oxidation in the hypothalamic AgRP neurons is necessary for AgRP neuronal function and fasting-induced food intake.
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