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

Background & Aims: 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 C57B1/6J vs obesity-resistant SW7R/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, SW7R/J mice exhibited a marked hyperphagia (calorie intake 60% higher than C57BI/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 naive mice. Furthermore, SW7R/J mice expelled nematodes more rapidly than C57BI/6J mice, an effect related to a T helper cell 2 immune response. Conclusions: C57B1 /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.