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, 4090% 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.