Background/Purpose:

An autoimmune response with differentiation and proliferation of immune cells and the subsequent tissue-directed inflammatory process in the symptomatic phase of the disease are very energy-demanding. As recent calculations demonstrate, the activated immune system needs approximately 20% of the basal metabolic rate. Thus, energy regulation and cellular bioenergetics are of outstanding importance to serve a stimulated immune system. During inflammation, particularly during the chronic process of inflammation in long standing inflammatory diseases like rheumatoid arthritis, a reallocation of energy-rich fuels to the activated immune system is necessary in order to nourish the inflammatory process. Energy consumption and, thus, ATP generation can be measured by studying the consumption of oxygen.

The energy expenditure in different organs at different time points has never been investigated during immunization. We want to find out if, and how the energy expenditure in different organs changes during the course of experimental arthritis.

Methods:

A new technique termed “spatial energy expenditure configuration (SEEC)” was developed to demonstrate bodily areas of high energy demand. SEEC is based on removal of tissue during the course of arthritis, and subsequent determination of oxygen consumption. For that purpose, small weighed pieces of the respective organ with a size of 4 mm are placed in 24-well multidishes with integrated oxygen sensors, which allows for non-invasive detection of oxygen consumption in vitro. SEEC was established in healthy control animals, arthritic animals and animals that underwent prior sympathectomy. The model of type II collagen arthritis in DBA/1 mice is used in order to develop an arthritic-specific SEEC.  We determined the oxygen consumption in spleen, thymus, draining lymph nodes, liver, kidney, brain and knee joints during the course of experimental arthritis for 70 days. The values are given in µmol O₂/l/h and refer to 4 mm sized pieces as percentage of mouse weight.

Results:

In draining lymph nodes of arthritic DBA/1J mice we observed a marked increase in oxygen consumption during the course of arthritis (200 %). Sympathectomy prior to immunization increases energy consumption in draining lymph nodes, which is most probably a sign of retention of leucocytes in the lymph node. C57BL/6 mice deficient for the important adipose triglyceride lipase revealed an increased oxygen consumption in the liver. This might be due to a lack of lipolysis activity, and therfore increased gluconeogenetic activity in the liver for the generation of energy rich fuels in form of glucose. ATGL-deficient  arthritic animals also showed higher energy demand in lymph nodes, adrenals and gut.

Conclusion:

The SEEC technique enables us to identify locations of high energy demand that are involved in the initiation and continuation of the autoimmune process in an animal model of arthritis. We identified the draining lymph nodes as target organ of the sympathetic nervous system, which will be further investigated. The technique will be applied to other chronic inflammatory disease models in order to detect further participating organs.

 

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« Back to ACR/ARHP Annual Meeting 2013

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-spatial-energy-expenditure-configuration-and-possible-applications-in-an-experimental-model-of-arthritis-2/