Divergent metabolic adaptations to intestinal parasitic nematode infection in mice susceptible or resistant to obesity.
OBJECTIVE
Diet-induced obesity results from increased ingestion of energy-dense food and sedentary lifestyle in genetically susceptible individuals. An environmental factor that may have shaped our energy homeostasis throughout evolution is parasitic nematode infection.


METHODS
To test the hypothesis that a metabolically "thrifty phenotype" is advantageous during intestinal nematode infection, we compared the responses to Heligmosomoides polygyrus infection between 2 mouse strains: obesity-prone C57Bl/6J vs obesity-resistant SWR/J. Metabolic phenotyping was performed using indirect calorimetry, dual energy x-ray absorptiometry, and magnetic resonance imaging scanning. Gene expression was assessed by quantitative reverse-transcription polymerase chain reaction and immunohistochemistry.


RESULTS
Body weight was maintained in both strains during nematode infection via different mechanisms. There was no apparent change in energy expenditure between the strains; however, SWR/J mice exhibited a marked hyperphagia (calorie intake 60% higher than C57Bl/6J) to maintain body weight. The importance of hyperphagia was confirmed by severe weight loss in a group of infected SWR/J mice whose food intake was restricted to that of naïve mice. Furthermore, SWR/J mice expelled nematodes more rapidly than C57Bl/6J mice, an effect related to a T helper cell 2 immune response.


CONCLUSIONS
C57Bl/6J mice are more energy efficient during parasitic nematode infection, which may explain their ability to tolerate the infection. SWR/J mice, on the other hand, require an increase in food intake to maintain energy stores during nematode infection. In addition, a strong T helper cell 2-mediated immune response that facilitates a prompt clearance of nematode infection in SWR/J mice may have evolved to conserve energy in this strain.
Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Tracie
T
Wong
Marie A
MA
Hildebrandt
Seana M
SM
Thrasher
Judith A
JA
Appleton
Rexford S
RS
Ahima
Gary D
GD
Wu
D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism; D007411:Intestinal Diseases, Parasitic / Q000378:metabolism / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009349:Nematode Infections / Q000378:metabolism / Q000503:physiopathology*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology