Proceedings of The Physiological Society

Future Physiology (Leeds, UK) (2017) Proc Physiol Soc 39, PC47

Poster Communications

Inhibition of Drp1 in the dorsal vagal complex of the brain reduces food intake in insulin resistant rats

B. Patel1, B. Filippi1

1. Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, United Kingdom.

Worldwide obesity has more than doubled since 1980, with over 600 million cases in 2014. Obesity can lead to many adverse metabolic effects of the cardiovascular, brain and endocrine systems. In rodents, the dorsal vagal complex (DVC) of the brain regulates glucose homeostasis and controls food intake through insulin signalling. A 3-day high fat diet (HFD) has shown to induce insulin resistance thus diminishing the DVC's ability to regulate glucose metabolism and food intake, though exact mechanistic effects of this are still unknown. HFD feeding is associated with an increase in mitochondrial fission in the DVC. Mitochondrial fission is regulated by dynamin related protein 1 (Drp1), high levels of Drp1 have been shown to correlate with increased levels of inducible nitric oxide synthase (iNOS), increased endoplasmic reticulum (ER) stress and insulin resistance in the DVC. In HFD fed rodents, molecular and chemical inhibition of Drp1 significantly improves the ability of DVC to regulate glucose metabolism. Whether increased mitochondria fission in the DVC of HFD fed rats affect food intake is still not known. Our data indicates that pharmacological inhibition of Drp1 with MIDVI-1 in the DVC reduced food intake in HFD fed rats as early as one day of injection. This data suggests that decreasing mitochondria fission in the DVC is sufficient to reduce hyperphagia in HFD fed rats.

Where applicable, experiments conform with Society ethical requirements