For years, it has been known that the immune system and metabolism are tightly coupled. For example, different fasting regimens have beneficial effects on various inflammatory and autoimmune diseases by affecting cells in the immune system. Furthermore, during infections cells of the immune system influence various metabolic reactions determining the severity of the infection. However, so far not much is known about how the cells of the immune system affect the metabolism of healthy individuals.
In a new study, Anne Loft and Søren Fisker Schmidt explored how liver macrophages signal to the highly specialized metabolic cells of the liver (hepatocytes). Here they found that liver macrophages during fasting are quite extensively remodeled leading to an altered communication with hepatocytes that influences the ability of the hepatocytes to produce fasting signals. “It is remarkable that the immune system – not only during infections - plays an important role in fine-tuning the metabolic reactions in the body”, postdoc and first author on the study, Anne Loft, states.
The researchers found that liver macrophages signal to the hepatocytes via a mechanism involving a transcriptional regulator named the glucocorticoid receptor (GR). Here they showed that fasting signals activate GR in liver macrophages, which affect the production of signaling molecules directed to the hepatocytes. For example, the production of the pro-inflammatory molecule, TNF, is suppressed in the liver macrophages, when GR is activated during fasting, which in turn promotes nuclear translocation and further activation of GR in hepatocytes. This mechanism then supports the production of ketone bodies in the hepatocytes, whose production is needed to ensure a constant energy supply to various tissues in the body during fasting. “We believe that our mechanism not only holds true during fasting but reveals a general principle by which the immune system can set the metabolic tone during inflammatory diseases and some metabolic disorders”, first and corresponding author, Søren Fisker Schmidt, states.
The paper is published in Cell Metabolism and the abstract as well as link to the full text version can be found here
Most of this work was carried out in the lab of Prof. Stephan Herzig at the Helmholtz Diabetes Center at Helmholtz Munich in collaboration with the Tuckermann lab at the Ulm University. Anne Loft is a Postdoctoral Researcher and Søren Fisker Schmidt is an Assistant Professor in the Center for Functional Genomics and Tissue Plasticity (ATLAS) funded by the Danish National Research Foundation.
Correspondence may be directed to Anne Loft anlo@bmb.sdu.dk or Søren Fisker Schmidt