Behavioural and molecular features of a rat model of diet-induced obesity
We established a rat model of diet-induced obesity (DIO). These rats develop a prediabetic phenotype characterized by hyperglycemia and hyperinsulinemia. Using a rat model of obesity and prediabetes allows us to simultaneously investigate changes in the brain, behavior, neuroendocrine hormones and other circulating factors, as well as innervation and metabolic function of peripheral tissues, in a comprehensive manner, which is challenging to do in human studies.
Project description
In collaboration with the Spatial Mass Spectrometry core facility at the Department of Pharmaceutical Biosciences at Uppsala University, we use a mass spectrometry imaging technique (MALDI-MSI) that allows for simultaneous mapping of multiple neuropeptides and neurotransmitters, and their precursors and metabolites, in the same brain tissue section. This makes it possible to measure changes in neurotransmitter pathways throughout the different brain regions during the development of obesity and insulin resistance in our DIO rat model. In combination with this, we use immunofluorescence brain histology imaging to assess e.g. receptor levels for targeted neurotransmitters (such as dopamine and serotonin receptors) as well as protein analysis in peripheral metabolically relevant tissues, with a focus on adipose tissue. Moreover, using tests, such as the Multivariate Concentric Square Field™ (MCSF) test, we can also study the impact of DIO on relevant behavioral traits.
The overall aim is to unravel novel mechanisms that promote obesity and T2D development. So, in addition to gaining mechanistic insight into disease-relevant processes, we also strive to carry out translational research. For this purpose, an important aspect of our work is that the findings from our preclinical model, can also be applied in humans and that ultimately may become targets for novel interventions.