CD163 - TRAIN project
TRAIN - Introduction
The epidemic increase in incidence of obesity has been paralleled by a rise in associated diseases such as type-2 diabetes and non-alcoholic fatty-liver disease (NAFLD).
Interestingly, only a subset of obese patients develop these chronic inflammatory diseases, and it is a present challenge to identify those subgroups of obese that need and may gain from intervention.
TRAIN will investigate the role of the specific immune effector cell – the macrophage - in obesity-associated life-style diseases. The macrophage cell is a hitherto underrated player in the development and chronic course of low-grade inflammatory diseases such as diabetes and atherosclerosis.
New data, however, suggests that the macrophage markers at an early stage can predict later chronic disease (diabetes and liver diseases) and treatment directed towards modulation of the macrophage activity may have pronounced effect on disease course.
We have previously identified the function and regulation in disease of the important macrophage receptor CD163, and we have now important hypothesis-generating data from a large prospective study of the general population showing that high plasma baseline levels of macrophage derived CD163 is associated with later several fold increased risk of developing obesity-related disease.
TRAIN now aims at exploring:
1) whether macrophage markers can be used to identify patient subgroups of obese with incipient disease (e.g. type-2 diabetes, NAFLD,
2) how these markers reflect the effects of intervention (e.g. weight loss, physical activity, medication),
3) how the acute inflammatory response of macrophages to obesity surgery (bariatric surgery) evolves, and
4) whether liver macrophages (Kupffercells) may function as therapeutic target in fatty liver disease.
We expect to develop new tools for identifying and monitoring patients at high risk for obesity related diseases and we expect to clarify whether modulation of the macrophage may be a new way of treating obesity-related diseases.