Drp1 is required for AgRP neuronal activity and feeding.

Sungho Jin, Nal Ae Yoon, Zhong-Wu Liu, Jae Eun Song, Tamas L Horvath, Jung Dae Kim, Sabrina Diano

eLife 2021 Mar 09

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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 Dnm1l in adult AgRP neurons (Drp1 cKO) show decreased 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, Drp1 cKO 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 body-weight regulation. © 2021, Jin et al.

Citation

Sungho Jin, Nal Ae Yoon, Zhong-Wu Liu, Jae Eun Song, Tamas L Horvath, Jung Dae Kim, Sabrina Diano. Drp1 is required for AgRP neuronal activity and feeding. eLife. 2021 Mar 09;10