Development of IR and GI in VAT-infection of obese mice
To accomplish research objective 1, we will combine DIO with acute and chronic infection models. Obesity causes a Th1-type inflammatory environment in VAT that is remarkably similar to that induced by viral infection. To enhance this Th1-type inflammation, mice will be virally infected.
LCMV is a systemic virus with a broad tropism, including the abdominal fat, which causes a strong, short-term infection that is completely cleared within 2 weeks after infection. Mice will be infected with LCMV at various stages during DIO, in order to investigate whether short-term infection has a long-term impact on VAT-inflammation and the onset of GI. Alternatively, our lab has experience with the use of acute intracellular bacterial infection models, such as Listeria Monocytogenes.
As a model for chronic VAT-infection, we will use mouse cytomegalovirus (mCMV). CMV is a herpes virus that induces a strong Th1-type immune response in mice and humans. Moreover, 40 – 90% of the population in the western world is infected with CMV, making it a very relevant human pathogen. CMV is never cleared from its host and stays lifelong latently present in infected tissues.
To gain mechanistic insight in pathogen-induced VAT-inflammation, we will elucidate which cell subsets play a detrimental role in induction of inflammation.