Evaluation of interactions between the metabolism and immune system in obesity using human cohort and intervention studies

Obesity is a global health problem, with COVID‑19 highlighting that affected individuals are not only at risk for chronic disease, but also for a severe course of acute infection. Thus, metabolic diseases have acquired an additional facet that requires scientific investigation. The aim of this dissertation was to investigate interactions between the metabolic and immune systems in obesity and associated comorbidities. Data from the cross-sectional Kiel FoCus cohort and data collected to assess weight loss from dietary and surgical bariatric intervention or severe infection were available to examine the involvement of the immune system in obesity pathogenesis, the extent of immunological impairment in manifest obesity, and the role of diet, immunologically active tissue and reversibility by weight loss. The effects of obesity on pathogen defense were also investigated.

A triangular relation between diet, immune system, and metabolism is evident with an unfavorable dietary composition impairing both immunological and metabolic functions. Neuroendocrine dysregulation of satiety in the hypothalamus due to inflammatory activity has been identified as a primary pathology that initiates a vicious cycle of energy-dense food preference, inflammatory progression, and weight gain. In severe obesity, this translates into increased risk of chronic non-communicable diseases, including immunopathologies, and acute communicable diseases. Adverse dietary composition emerged, via direct and indirect effects through the gut microbiota as an important determinant. The accumulation of free fatty acids, impairment of immunologically active lung cells, and changes in the hematopoietic immune cell reservoir were also relevant.

There were strong parallels to immunosenescence in older age proposing an acceleration of immunological aging in obesity, whereby the reversibility of seen alterations holds great potential for future obesity medicine.


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