THE FILIPPI LAB
Insulin sensing and resistance in the brain
We Study how insulin in a specific area of the brain called the Dorsal Vagal Complex (DVC) modulates glucose metabolism and feeding behaviour in normal, obese and diabetic rodent models. We use in vivo techniques that require surgical implants in rats in order to inject specific treatments in the brain, and in vitro biochemical and molecular biology techniques. We aim to uncover the molecular mechanism behind insulin signalling and resistance in the brain.
INSULIN SENSING IN THE DVC
The Dorsal Vagal Complex (DVC) of the brain senses insulin to control metabolic functions. The neuronal network involved in this process is still unknown.
We aim to characterise the neuronal population and the neuronal relay that transduces insulin signal from the DVC to the peripheral organs.
MITOCHONDRIA DYNAMICS AND INSULIN RESISTANCE IN THE DVC
Within 3 days of high-fat diet feeding our rodent models become insulin resistant and the DVC loses the ability to sense insulin. This is due to changes in mitochondria dynamics. In detail, there is an increase in mitochondria fission that causes insulin resistance and impairs the ability of the DVC to control glucose metabolism.
We aim to characterise the effect that changes in mitochondria fission have on feeding behaviour, body weight, fat deposition and brown fat activity.
MOLECULAR MECHANISM OF INSULIN RESISTANCE
Within 3 days of high-fat diet feeding our rodent models become insulin resistant and the DVC loses the ability to sense insulin and control metabolic functions. We aim to characterise the molecular mechanism that causes insulin resistance by using proteomics and transcriptomics.
RESEARCH FELLOW IN NEUROSCIENCES, A POST DOC POSITION IN OUR LAB.
We are looking for a Post-Doc that would like to join our laboratory. Is a fixed-term position, for more information please click on the link below.
PHD STUDENT POSITION
How GABA neurones in the DVC control glucose metabolism
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.