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.