The Metabolic Response
To Colitis Varies Depending Upon Whether Inflammation Is Chronic Or
Acute
(BETHESDA, MD) – A new study being published by
the American Physiological Society (www.The-APS.org)
finds that the body responds differently to colitis (inflammation of the
colon) based on whether the disease is acute (sharp and brief) or chronic
(long-term). Researchers, using an experimental mouse model of colitis,
discovered that the effects of acute colitis were associated with decreased
body weight, food intake, and body fat content. Chronic colitis was
associated with reduced body fat content, decreased bone mineral density and
attenuated use of energy, termed energy expenditure. The discovery may help
lead to better symptom management for the 500,000 Americans who live with
the disease.
The study, “Mice With Experimental Colitis Show an
Altered Metabolism With Decreased Metabolic Rate, ” was conducted by Silvia
Melgar and Erik Michaëlsson, Integrative Pharmacology, GI Biology,
AstraZeneca; Lennart Svensson, Department of Molecular Pharmacology,
AstraZeneca; Anna-Karin Gerdin and Mohammad Bohlooly-Y, AstraZeneca
Transgenics and Comparative Genomics Centre, AstraZeneca, Molndal, Sweden;
and Mikael Bjursell, Department of Physiology/Endocrinology, Institute of
Neuroscience and Physiology, The Sahlgrenska Academy, Goteborg University,
Sweden and AstraZeneca Transgenics and Comparative Genomics Centre,
AstraZeneca, Molndal, Sweden. Their study appears in the Articles in Press
Section of the American Journal of Physiology, Gastrointestinal and
Liver Physiology. The journal is one of 11 peer reviewed scientific
publications issued each month by the American Physiological Society (APS).
The Study
Using dextran sulfate sodium (DSS), the researchers
chemically induced the symptoms of colitis into three groups of mice. The
first group (n=14) was given DSS for seven days, thus inducing acute
inflammation. The second group (n=16) received DSS for five days followed
by three weeks of water in order to induce chronic inflammation. The third
group (controls) (n=13) received only water. After being fed DSS, some
portion of each group was treated with an anti-inflammatory substance (acute
group: n=6; chronic group: n=4; control: n=6) to investigate the potential
effect(s) on bone metabolism.
The mice were examined using a series of tests,
including body composition review, indirect calorimetry and
sampling of tissue, plasma and feces for analysis. Values were
considered statistically significant at p<0.05.
Results
Highlights of the researchers’ findings include:
Inflammation and clinical symptoms: Mice exposed
to seven days of DSS developed acute inflammation, characterized by
decreased body weight, loose feces/diarrhea, and visible fecal blood. Mice
with chronic inflammation started to decrease their body weights during DSS
treatment and continued to do so for one week after being removed from DSS.
However, they slowly recovered their weight, reaching their initial weights
three weeks after resuming water-only consumption.
The inflammatory score and the
levels of local pro-inflammatory markers were lower for mice with acute
inflammation than for those with chronic inflammation as compared to
controls. In addition, levels of systemic inflammatory markers were
elevated in mice with acute or chronic inflammation compared to controls.
Metabolic rates: Mice with acute inflammation
tended to have reduced resting energy expenditure. On the other hand, mice
with chronic inflammation had significantly decreased resting energy
expenditure.
The data also suggested that
mice with acute inflammation used fat as an energy source compared to
chronically inflamed mice, which used nutrients in similar to healthy
control mice.
Food/water intake: Mice with acute inflammation
showed a significantly decreased food and water intake and tended towards
reducing their activity, in line with tendency towards lower energy
expenditure. In contrast, mice with chronic inflammation tended towards
increased food and water intake, while having significantly lower activity –
in correlation to lower energy expenditure. In addition, both acute and
chronic inflamed mice had reduced energy assimilation from feces.
Body composition: Body fat was reduced in mice
during the acute inflammatory phase and remained at reduced levels during
the chronic phase, despite the fact the mice had returned to normal eating
patterns. The lean mass of the chronic mice was normalized to the levels of
healthy control mice.
Metabolic plasma markers: Glucose, leptin, T4,
and albumin levels were significantly decreased in mice regardless of
whether they had acute or chronic inflammation. The blood plasma markers for
lipid metabolism (triglyceride and cholesterol) were different. In mice with
acute inflammation, the triglyceride levels were reduced, whereas
cholesterol levels were increased among chronically inflamed mice.
Conclusions
This study shows that mice with acute colitis (colon
inflammation) had decreased body weights, lower fat and lean mass, reduced
intakes of food and water, and a tendency towards lower levels of activity
and energy expenditure. By contrast, mice with chronic inflammation
recovered from their bout, and had food intake, body weight and lean mass
comparable to the controls, but their energy expenditure, activity and body
fat content were still significantly reduced. To cope with the chronic
inflammatory condition, the researchers observed that the mice undergo
profound metabolic changes. Further research is necessary to better
understand why and how.
***
JOURNAL PUBLICATION INFORMATION
American Journal of Physiology, Gastrointestinal and
Liver Physiology.
NOTE TO EDITORS
To schedule an interview with a member of the research
team, please contact Donna Krupa at 301.634.7209 (direct dial), 703.967.2751
(cell) or
dkrupa@The-APS.org.
Physiology is the study of how molecules, cells,
tissues and organs function to create health or disease. The American
Physiological Society (APS) has been an integral part of this scientific
discovery process since it was established in 1887.
