THE FILIPPI LAB

OUR MOST RECENT WORK IN BIORXIV: "MANIPULATING MITOCHONDRIAL DYNAMICS IN THE NTS PREVENTS DIET-INDUCED DEFICITS IN BROWN FAT MORPHOLOGY AND ACTIVITY" FOZZATO ET AL 2023

Brown adipose tissue (BAT) is a potent thermogenic organ, activated by direct adrenergic sympathetic discharge from the central nervous system and circulating glucose and fatty acids. We showed that short term HFD-feeding decreases BAT ability to uptake glucose, alters noradrenergic discharge, by downregulating the availability of noradrenaline precursor Tyrosine Hydroxylase (TH) within BAT, and increases infiltration of enlarged white fat droplets in the BAT. It is sufficient to inhibit mitochondrial fragmentation in the nucleus of the tractus solitarius (NTS) astrocytes of HFD-fed rats to prevent the effects on BAT morphology and innervation and increase BAT’s glucose uptake. This effect is associated to a decrease in blood glucose and insulin levels. In regular chow-fed rats, increasing mitochondrial fragmentation in the NTS astrocytes reduces BAT glucose uptake and TH levels. In summary targeting mitochondrial dynamics in the NTS-astrocytes could be a good strategy to increase energy expenditure and protect from developing obesity and diabetes.