Divergent metabolic adaptations to intestinal parasitic nematode infection in mice susceptible or resistant to obesity

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 133; no. 6; p. 1979
• Main Authors: Wong, Tracie, Hildebrandt, Marie A, Thrasher, Seana M, Appleton, Judith A, Ahima, Rexford S, Wu, Gary D
• Format: Journal Article
• Language: English
• Published: United States 01.12.2007
• Subjects: Animals; Disease Models, Animal; Energy Metabolism; Intestinal Diseases, Parasitic - metabolism; Intestinal Diseases, Parasitic - physiopathology; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Male; Mice; Mice, Inbred C57BL; Nematode Infections - metabolism; Nematode Infections - physiopathology; Obesity - metabolism; Obesity - physiopathology
• ISSN: 1528-0012
• DOI: 10.1053/j.gastro.2007.09.006

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. 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. 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. 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.