Short-Term Re-Feeding of Previously Energy-Restricted C57BL/6 Male Mice Restores Body Weight and Body Fat and Attenuates the Decline in Natural Killer Cell Function after Primary Influenza Infection

A hallmark of energy restriction (ER) is a decrease in total body fat, which is thought to increase lifespan and maintain immune function. However, we have shown that during primary influenza infection, ER induces rapid weight loss, impairs natural killer (NK) cell function, and increases mortality in young and aged mice. To determine whether influenza-induced NK cell function could be restored in ER mice, young adult (6 mo) male C57BL/6 mice were fed an ER diet or re-fed (RE) control diet ad libitum for 2 wk before infection with PR8 influenza A. An initial hyperphagic response was observed in RF mice, characterized by increased food intake, rapid weight gain, and restoration of body fat and fat depots by 5-7 d of re-feeding to levels comparable to control ad libitum (AL) mice. Re-feeding improved survival and attenuated the decline in NK cell function during infection, evidenced by increased numbers, percentages, and CD69 expression by d 3 postinfection in RE mice. Interestingly, an altered metabolic phenotype was observed during infection of RF mice, with plasma leptin concentrations greater than in ER mice but less than in AL mice. In contrast, adiponectin concentrations of RE mice were lower than those of both ER and AL mice. These data suggest that re-feeding for a defined period before, and perhaps throughout, influenza season may provide the energy needed to counter the deleterious effects of ER on NK cell function, especially during exposure to newly emerging strains of influenza, for which vaccines are limited or unavailable. J. Nutr. 140: 1495-1501, 2010.