Food Restriction Prolongs Murine Cardiac Grafts

• We investigated the correlation of energy restriction and immunosuppression.
• Energy restriction prolonged murine cardiac allograft survival.
• Energy restriction may induce impairment of alloimmune response.
• Energy restriction may lead to lower generation of regulatory T cells.

Overeating and obesity lead to cardiovascular disease, diabetes, and eventually premature death, whereas food or energy restriction reduces risk factors for cardiovascular disease and diabetes and expands the life span. The aim of this study was to investigate the effect of food restriction (FR) in a murine heart transplant model. CBA male recipients (H2k) that underwent transplantation of C57BL/6 (H2b) hearts were assigned to free access group or FR groups with food intake at 60% (40% FR), 50% (50% FR), or 40% (60% FR) of the average food intake for 1 week after transplantation, and each median survival time was measured. We also performed cell proliferation, cytokine production, and flow cytometry assessments. The 60% FR CBA recipients showed prolongation of allograft survival (median survival time, 24 days). Cell proliferation and interferon-γ were suppressed in the 60% FR CBA recipients. Flow cytometry studies showed a lower CD4+CD25+Foxp3+ cell population in splenocytes from the 60% FR CBA recipients. In conclusion, the findings suggest that the prolongation of cardiac allograft resulted from not regulation of alloimmune responses, but partial impairment of alloimmune responses, linking energy restriction to low generation of splenic CD4+CD25+Foxp3+ regulatory T cells.