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.
OUR RESEARCH
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.
NEWS
OUR MOST RECENT WORK PUBLISHED IN MOLECULAR METABOLISM!!!
1.New, L. E. et al. Insulin evokes release of endozepines from astrocytes of the NTS to modulate glucose metabolism in male rats. Mol. Metab. 101, 102255 (2025).
https://www.sciencedirect.com/science/article/pii/S2212877825001620
Highlights
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Insulin receptors in astrocytes are essential for the NTS's regulation of hepatic glucose production.
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Insulin stimulates the release of endozepines (DBI/ODN) from astrocytes, and ODN injection into the NTS reduces hepatic glucose production.
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The action of endozepines in the NTS is mimicked by GABAA antagonists and inhibited by a GABAA agonist.
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Injection of ODN or Gabazine into the NTS of HFD-fed rats bypasses insulin resistance and decreases hepatic glucose production.
CONTACT US
Faculty of Biological Sciences, School of Biomedical Sciences
Garstang Building,
Room 6.41e
University of Leeds,
Leeds,
west Yorkshire
LS2 9JT
UK
+44 113 343 4424‬