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Brief refeeding rapidly reverses dietary restriction-induced nuclear factor-kappaB downregulation in peritoneal
Woodae Kang1, Hideaki Saito, Kazuhiko Fukatsu
1Surgical Center, University of Tokyo, Japan. kang-woodae@umin.ac.jp
Background:
Malnutrition impairs host immunity, resulting in high mortality and morbidity, secondary to infections. Nuclear factor kappaB (NFkappaB) plays a critical role in host defense, but how quickly refeeding normalizes the impaired NFkappaB activity in peritoneal resident cells (PRCs) is unknown. Our aim was to investigate the effects of 1-day ad libitum refeeding on severe diet restriction-induced NFkappaB activity in PRCs.
Methods:
Mice received chow, 146 g/kg per day (ad libitum) or 36.5 g/kg per day (severe diet restriction), for 7 days. One-half the mice in the diet-restricted group were then fed ad libitum for 1 day (refeeding). PRCs were harvested by peritoneal lavage. After incubation with tumor necrosis factor-alpha (TNF-alpha), nuclear translocation of NFkappaB in PRCs was investigated using laser scanning cytometry.
Results:
The main subpopulation of PRCs was macrophages in all groups. Mean fluorescence intensity over the nuclear area at 0 or 100 ng/mL of TNF-alpha was 16 +/- 2 or 31 +/- 8* in the ad libitum, 20 +/- 4 or 19 +/- 3 in the severe diet-restricted, and 20 +/- 4 or 30 +/- 5* in the refeeding group, respectively (*p < .05 versus 0 ng/mL of TNF-alpha in each group versus 100 ng/mL of TNF-alpha in diet-restricted group). Cytoplasmic accumulation of NFkappaB was significantly increased after TNF-alpha stimulation in the refed group but not in the ad libitum group.
Conclusions:
The blunted NFkappaB activity in PRCs, after exposure to inflammatory stimuli, was restored after 1 day of refeeding, with increased accumulation of NFkappaB in the cytoplasm. Even brief nutritional replenishment in malnutrition may improve host defense by restoring NFkappaB activity and thereby improving macrophage functions.