In this fellowship, we showed that by simply increasing mitochondria fission in the DVC we cause insulin resistance, hyperphagia, and body weight gain while inhibition of mitochondria fission on the DVC of high-fat diet-fed, insulin resistant, rats protects from developing insulin resistance, decreases body weight and food intake. This data makes mitochondria fission and the protein that regulates it (DRP1) a potential target for restoring insulin sensitivity in obese and diabetic individuals.
With mitochondria fission, we also see an increase in the levels of a protein called inducible Nitric oxide synthase (iNOS). This is an enzyme that can regulate the activity of many different proteins and is involved in changes in insulin signalling. With this fellowship, we also discovered that by decreasing iNOS levels in high-fat diet-fed rats, we can prevent the development of insulin resistance, decrease body weight and food intake. This also makes iNOS a potential drug target to fight insulin resistance in obesity and diabetes.
We have a manuscript in preparation that contains the aforementioned results and that we hope to submit soon.
The DVC is an important brain centre that receives signals from the peripheral organs and relays these signal to higher areas of the brain. In addition, the DVC can also receive signals from other brain areas and relay them to the peripheral organs. Due to his nature, the DVC has a highly diversified group of neuronal cells. An important question that is still unanswered is which neuronal population in the DVC is involved in insulin sensing and regulates feeding behaviour. In the attempt to address this question we performed a histochemical characterization of the DVC neuronal populations. The data we obtained will be used in the future to target specific neuronal cell types in the DVC in order to understand their involvement in sensing insulin.
This work was presented in a series of scientific meetings:
Invited seminar and talks:
Mitochondria Form and Function, 14-15 September 2017, London, sponsored by the physiological society. I was part of the organization committee that selected the theme and the speakers and I also gave a talk: Filippi B.M.: Mitochondria fission in the dorsal vagal complex induces insulin resistance. Mitochondria: Form and Function meeting, 14 -15 September 2017, London, UK (Invited Speaker)
Filippi B.M.: Mitochondria fission in the dorsal vagal complex induces insulin resistance. Institute of Hepatology, 14 November 2017, London, UK) (Invited seminar)
Posters presentations:
Future Physiology, University of Leeds, LS2 9JT, Inhibition of Drp1 in the Dorsal Vagal Complex of the Brain Reduces Food Intake in Insulin Resistant Rats PC47 (Nov 17)
Mitochondrial Medicine, Wellcome Genome Campus, Hinxton,CB10 1SA: Inhibition of mitochondrial fission in the Dorsal Vagal Complex of the Brain prevents Hyperphagia in High Fat Diet Fed Rats P69 (May 18)
Europhysiology, QEII, London, SW1P 3EE: Inhibition of mitochondrial fission in the Dorsal Vagal Complex of the Brain prevents Hyperphagia in High Fat Diet Fed Rats PCA299 (Sep 18)
SFN, San Diego Convention Centre, San Diego, CA 92101: Inhibition of mitochondrial fission in the Dorsal Vagal Complex of the Brain prevents Hyperphagia in High Fat Diet Fed Rats XX3 (Nov 18)
Public engagement:
When we show our data to the public we create awareness about the danger of being overweight and having an unhealthy lifestyle and the negative effect that this has on the brain and consequently in the body. I presented these findings in public events:
- In the "Pint of Science" I interacted with an adult audience and talked about the brain and how it regulated metabolic functions. I disseminate awareness of the dangers of obesity and insulin resistance and how they can lead to the development of diabetes.
- In the be Curious (A day event at the University of Leeds open to children and families), we had a stall in which we interacted with the young generation and talked about sugars and how they are metabolised and how they can be dangerous.
