Thesis Henk Schipper: “Adipose tissue as an immunological organ – Implications for childhood obesity”


Thesis: Adipose tissue as an immunological organ – Implications for childhood obesity

Author: Henk Schipper – Pediatric immunology department (‘Prakken group’) – Wilhelmina Children’s Hospital Utrecht, The Netherlands


The immunological actions of adipose tissue (AT) are highly relevant for children with rheumatoid disorders like Juvenile Idiopathic Arthritis (JIA), next to obese children. As described in this thesis, adipose tissue propagates local and systemic inflammation in response to distinct stimuli, including systemic inflammation. The responsiveness of adipose tissue to systemic inflammatory processes is explained from a bioenergetic perspective by the energy-on-demand model: in case of infection, adipose tissue inflammation promotes the mobilization of nutrients via gluconeogenesis, hyperglycaemia, and lipolysis, which serves to fuel the activated immune system. This energy-on-demand mechanism is highly profitable in case of acute bacterial infections that require an immediate immune response, but deleterious for the host in case of chronic inflammatory disorders. Chronic inflammation in rheumatoid disorders such as JIA seems to drive chronic adipose tissue inflammation, thus promoting continuous mobilization of glucose and lipids, and at last the development of insulin resistance, type 2 diabetes, and cardiovascular disease. The energy-on-demand model illustrates the way an adaptive strategy against infection can turn against itself: multiple groups documented a high prevalence of insulin resistance, type 2 diabetes and cardiovascular disease in patients with systemic rheumatic disorders.  

In this thesis, several inflammatory mechanisms in adipose tissue are unravelled. Special focus is on the role of natural killer T (NKT) cells, which were recently shown to communicate with adipocytes in a CD1d-dependent manner, and play a key role in maintaining healthy adipose tissue (JCI, 2012). Furthermore, the role of adipose tissue-secreted proteins (adipokines) such as adiponectin, leptin, chemerin and cathepsin S is discussed in detail. More information is available online ( and on request (


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