S.M. van den Berg
- A hot interaction between immune cells and adipose tissue
M.P.J. de Winther
- Award date
- 2 June 2017
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Systemic as well as adipose tissue inflammation contributes to the development of obesity-associated diseases. This thesis describes three targets to battle this chronic inflammation in a model of diet-induced obesity in mice. First, we studied inflammation in obese white - and brown adipose tissue and whether the immune system contributes to adaptive thermogenesis. We show that short-term high-fat diet causes an accumulation of lipids, macrophages infiltration and pro-inflammatory cytokines and chemokines in brown adipose tissue. Furthermore, a high-fat diet leads to a rapid decline in eosinophils within both white - and brown adipose tissue. We identify an interesting crosstalk between immune cell cytokines and brown adipocyte derived chemokines, which is involved in the regulation of brown adipocyte activity. However, short-term treatment with helminth antigens in high-fat diet-fed mice induces an adipose depot-specific type 2 immune response which does not contribute to thermogenic activation. We then explored how the chronic low-grade inflammatory state in obesity and the continuous recruitment of immune cells affects hematopoietic stem cells in the bone marrow. Obesity induces long-term alterations on hematopoietic stem cells including loss of stemcellness, increased differentiation potential and reduced proliferation. Lastly, we demonstrate that inhibiting the interaction between the co-stimulatory molecule CD40 and its adaptor protein TRAF6 using a small-molecule inhibitor improves glucose tolerance and reduces adipose tissue immune cells in diet-induced obese mice.
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