Manipulating mitochondrial dynamics in the NTS prevents diet-induced deficits in brown fat morphology and glucose uptake

Abstract

Brown adipose tissue (BAT) uptakes and metabolises both glucose and triglycerides to produce heat and is activated by the central nervous system (CNS) through direct noradrenergic sympathetic innervation. Dysregulation of signalling modules 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. Our findings demonstrated that short-term HFD feeding reduces BATs ability to take up glucose, as measured by PET/CT scan. However, inhibiting mitochondrial fragmentation in NTS-astrocytes of HFD-fed rats improved BAT glucose uptake while lowering blood glucose and insulin levels. Compared with HFD-fed rats, HFD fed animals, where mitochondrial fragmentation was inhibited in the NTS-astrocytes, had higher levels of catecholaminergic innervation of BAT, and did not present 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, catecholaminergic innervation and {beta}3-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.