Digestive Health Center

  • Obesity and the Digestive System

    Senad Divanovic, PhD
    Instructor
    Department of Pediatrics; Division of Cellular and Molecular Immunology

    Description of Research

    Dr. Divanovic’s research program focuses on understanding the molecular mechanisms underlying the regulation of innate immune signaling and inflammation in mouse models of obesity, obesity-associated non-alcoholic fatty liver disease (NAFLD) and infectious diseases. Related to this grant, his studies range from reductive analysis of TLR ligand signaling and challenge to mouse models of obesity and infection. Further, he is using experimental models of obesity to test the hypothesis that obesity-driven upregulation of IL-17 production is central to the pathogenesis of NAFLD. 

    Collaborations

    Dr. Divanovic has used the Integrative Morphology Cores in collaboration with Drs. Kohli, and Hoebe in animal-based experiments to interrogate the pathogenic mechanisms of NAFLD. Further, Dr. Divanovic is using liver tissue samples from obese adolescents, provided by the Obesity Tissue Repository at CCHMC, in collaboration with Dr. Xanthakos for validation and correlation of specific hypotheses to human disease. Anticipated Core Use: Gene and Protein Expression, Bioinformatics, and Integrative Morphology Cores.

 
  • Research image.

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    Research image.

    Increased steatosis but decreased steatohepatitis in IL-17RA deficient mice on a high fat diet (HFD). Liver sections after 20 week on HFD show marked differences in the level and type of steatosis between WT and IL-17RA-/- mice on HFD (A). HFD stress drives macrovesicular steatosis (black arrows), predominantly located in zone 3 (outlined in white), with sparing of zone 1 (black circles) in WT controls. In contrast, IL-17RA-/- mice show increased overall steatosis that is predominantly microvesicular (red arrows). (B) Lobular inflammation (white arrows) in the livers of WT mice on HFD is absent in IL-17RA-/- livers. Preliminary data presented in Pilot and Feasibility application.