内科学
内分泌学
生物
褐色脂肪组织
葡萄糖摄取
白色脂肪组织
产热素
瘦素
线粒体
酪氨酸羟化酶
碎片(计算)
脂肪组织
胰岛素
细胞生物学
肥胖
医学
多巴胺
生态学
作者
Arianna Fozzato,Lauryn E New,Joanne C. Griffiths,Bianca Patel,Susan A. Deuchars,B Filippi
出处
期刊:Life Sciences
[Elsevier]
日期:2023-09-01
卷期号:328: 121922-121922
被引量:3
标识
DOI:10.1016/j.lfs.2023.121922
摘要
Brown adipose tissue (BAT) can produce heat by metabolizing glucose and fatty acids. Activation of BAT is controlled by the central nervous system (CNS) through sympathetic innervation. Dysregulation of signalling molecules in selective CNS areas such as the nucleus of tractus solitarius (NTS) are linked with altered BAT activity, obesity and diabetes. High-fat diet (HFD)-feeding increases mitochondrial fragmentation in the NTS, triggering insulin resistance, hyperphagia and weight gain. Here we sought to determine whether changes in mitochondrial dynamics in the NTS can affect BAT glucose uptake.Rats received DVC stereotactic surgery for local brain administration of viruses that express mutated Drp1 genes. BAT glucose uptake was measured with PET/CT scans. Biochemical assays and immunohistochemistry determined altered levels of key signalling molecules and neural innervation of BAT.We show that short-term HFD-feeding decreases BAT glucose uptake. However, inhibiting mitochondrial fragmentation in NTS-astrocytes of HFD-fed rats partially restores BAT glucose uptake accompanied by lower blood glucose and insulin levels. Tyrosine Hydroxylase (TH) revealed that rats with inhibited mitochondrial fragmentation in NTS astrocytes had higher levels of catecholaminergic innervation in BAT compared to HFD-fed rats, and did not exhibit HFD-dependent infiltration of enlarged white fat droplets in the BAT. In regular chow-fed rats, increasing mitochondrial fragmentation in the NTS-astrocytes reduced BAT glucose uptake, TH immune-positive boutons and β3-adrenergic receptor levels.Our data suggest that targeting mitochondrial dynamics in the NTS-astrocytes could be a beneficial strategy to increase glucose utilization and protect from developing obesity and diabetes.
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