Effect of severe calorie restriction on the lung in two strains of mice

Abstract

There is a body of literature in animal models that has suggested the development of emphysema following severe calorie restriction. This has led to the notion of "nutritional emphysema" that might have relevance in COPD patients. There have been few studies, however, that have looked closely at both the mechanics and lung structure in the same animals. In the present work, we examined lung mechanics and histological changes in two strains of mice that have substantial differences in alveolar size, the C57BL/6 and C3H/HeJ strains. We quantified the dynamic elastance and resistance at 2.5 Hz, the quasistatic pressure volume curve, and the alveolar chord lengths in lungs inflated to a lung capacity at 25-30 cm H(2)O. We found that after 2 or 3 wk of calorie restriction to 1/3 their normal diet, the lungs became stiffer with increased resistance. In addition, the lung capacity was also decreased. These mechanical changes were reversed after 2 wk on a normal ad libitum diet. Histology of the postmortem fixed lungs showed no changes in the mean alveolar chord lengths with calorie restriction. Although the baseline mechanics and alveolar size were quantitatively different in the two strains, both strains showed similar qualitative changes during the starvation and refeeding periods. Thus, in two strains of mice with genetically determined differences in alveolar size, neither the mechanics nor the histology show any evidence of emphysema-like changes with this severe caloric insult.

Fig. 1.

Mean (±SE) percent weight loss during 3 wk of calorie restriction (CR) to 1/3 of the normal diet in B6 (•) and C3 (○) mice. There were no significant differences in the rate of weight loss between these strains.

Fig. 2.

Mean (± SE) deflation limbs of the quasistatic pressure-volume curve in C3 and B6 mice in controls, after 2–3 wk of CR, and after 2 wk of refeeding. There were no differences between control and refed groups, but there was a significant decrease in the CR group for each strain (P < 0.001 for both).

Fig. 3.

Mean (± SE) respiratory system resistances in control, CR, and refed groups in B6 and C3 strains. There was a significant increase in resistance in both strains at the end of the period of CR (P < 0.001 for each strain) that reversed after refeeding.

Fig. 4.

Mean (± SE) dynamic elastances in control, CR, and refed groups in B6 and C3 strains. There was a significant increase in resistance in both strains at the end of the period of CR (P < 0.001 for each strain) that reversed after refeeding.

Fig. 5.

Top: mean (± SE) quasistatic compliance determined from the deflation limb of pressure-volume curve between 0 and 10 cmH₂O in control, CR, and refed groups in B6 and C3 strains. There were significant differences in both strains with CR (P < 0.05 and P < 0.01 for B6 and C3, respectively). Bottom: the specific compliance [values at left normalized to lung volume (V₃₅)]. There were no significant changes in the specific elastance in either strain with CR or refeeding.

Fig. 6.

Representative sections taken at 1.5 μm/pixel from B6 and C3 strains before and after CR. The alveoli are clearly larger in the C3, but there is no qualitative evidence of any effect of CR. Bar marker is 200 μm.

Fig. 7.

Mean and individual animal air space chord lengths (Lm) in control, CR, and refed groups in B6 and C3 strains. Control values of Lm were higher in the C3 strain (P < 0.001), but there was no significant effect of CR in either strain after CR or refeeding.

Fig. 8.

Mean (± SE) respiratory alveolar surface area in control, CR, and refed groups in B6 and C3 strains. There were significant decreases in surface area in both strains at the end of the period of CR (P < 0.01 and P < 0.05, respectively), which reversed after refeeding.