IFN-γ produced in infection down-regulates PPAR-γ to modulate adipose tissue biology Mia Krapić1, Inga Kavazović1, Tamara Turk Wensveen2,3, Felix M. Wensveen1 1 Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia 2 Center for Diabetes, Endocrinology and Cardiometabolism, Thalassotherapia, Opatija, Croatia 3 Department of Internal Medicine, Faculty of Medicine, University of Rijeka, Rijeka, Croatia. Adipose tissue is a major lipid storage organ which releases and distributes lipids to maintain energy homeostasis. In context of metabolic disease, adipose tissue was shown to closely interact with the immune system as obesity drives inflammation in this organ which alters local and systemic regulation of metabolism. However, how immune cells interact with adipocytes in context of viral infection is largely unknown. Here, we investigated the impact of virus-induced activation of the immune system on adipose tissue metabolism and the underlying benefit of these changes to the organism. In an in vitro model of adipocyte differentiation, we could show that the pro-inflammatory cytokine IFN-γ significantly reduces cellular lipid content. High-throughput transcriptome analysis of these cells demonstrated that IFN-γ mediates down-regulation of PPAR-γ, a master regulator of adipocyte tissue metabolism, as well as many of its downstream targets, causing a net efflux of nutrients. Infection of mice with cytomegalovirus induced a striking reduction of adipocyte cell size and induced a change in the transcriptional profile of these cells corresponding with an IFN-γ imprint. Accordingly, infection caused a systemic increase of adipose tissue derived nutrients, such as free fatty acids in circulation. Importantly, our results indicate that these nutrients promote the acute lymphocyte response to viral infection. Our findings suggest that cytokines produced in response to viral infection can modulate adipocyte and systemic metabolism to benefit the immune response to infectious disease.
Department of Histology and Embryology, Faculty of Medicine, University of Rijeka
You must be logged in and own this session in order to