Tak1 licenses mitochondrial transfer from astrocytes to POMC neurons to maintain glucose and cholesterol homeostasis

Autor: Kaili Yin, Tingting Zhang, Xiyuan Lu, Qing Shen, Kaiyue Gu, Ying Huang, Chaonan Li, Jingyi Hou, Juxue Li, Guo Zhang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cell Reports, Vol 43, Iss 12, Pp 114983- (2024)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2024.114983
Popis: Summary: It remains incompletely understood how the astrocytes in the mediobasal hypothalamus (MBH) regulate systemic glucose and cholesterol metabolism. Here, we show that MBH astrocytic Tak1 (transforming growth factor β [TGF-β]-activated kinase 1) controls the metabolism of glucose and cholesterol. Tak1 is expressed in MBH astrocytes and activated after a short-term nutritional excess. In chow-fed mice, astrocytic deletion of Tak1 across the brain or its suppression in the MBH impairs glucose tolerance, reduces insulin sensitivity, and results in hypercholesterolemia. Astrocytic Tak1 activation in the MBH alleviates these symptoms in mice fed a high-fat diet (HFD). We show that astrocytic Tak1 modulates the activity of proopiomelanocortin (POMC) neurons and enables the transport of mitochondria from astrocytes to POMC neurons. In astrocytic Tak1 knockout mice, supplementation of CD38, a molecule that is crucial in mitochondrial transfer, restores glucose and cholesterol homeostasis. Overall, these findings highlight an important role of MBH astrocytic Tak1 in glucose and cholesterol metabolism.
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