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bioRxiv · 10.1101/2020.10.11.335224

DRP1 IS REQUIRED FOR AGRP NEURONAL ACTIVITY AND FEEDING

Jin, S.·Yoon, N. A.·Liu, Z.-W.·Horvath, T.·Kim, J. D.·Diano, S.
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Abstract

The hypothalamic orexigenic Agouti-related peptide (AgRP)-expressing neurons are crucial for the regulation of whole-body energy homeostasis. Here, we show that fasting-induced AgRP neuronal activation is associated with dynamin-related peptide 1 (Drp1)-mediated mitochondrial fission and mitochondrial fatty acid utilization in AgRP neurons. In line with this, mice lacking Drp1 in adult AgRP neurons (Drp1AgRPKO) show decrease in fasting-or ghrelin-induced AgRP neuronal activity and feeding and exhibited a significant decrease in body weight, fat mass, and feeding accompanied by a significant increase in energy expenditure. In support of the role for mitochondrial fission and fatty acids oxidation, Drp1AgRPKO mice showed attenuated palmitic acid-induced mitochondrial respiration. Altogether, our data revealed that mitochondrial dynamics and fatty acids oxidation in hypothalamic AgRP neurons is a critical mechanism for AgRP neuronal function and associated behavior.

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Jin, S., Yoon, N. A., Liu, Z.-W., Horvath, T., Kim, J. D., Diano, S.. 2020-10-11. DRP1 IS REQUIRED FOR AGRP NEURONAL ACTIVITY AND FEEDING. https://doi.org/10.1101/2020.10.11.335224

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