High-fat diet–induced obesity enhances allograft rejection

LL Molinero, D Yin, YM Lei, L Chen, Y Wang… - …, 2016 - journals.lww.com
LL Molinero, D Yin, YM Lei, L Chen, Y Wang, AS Chong, ML Alegre
Transplantation, 2016journals.lww.com
Background Obesity promotes a state of low-grade inflammation that exacerbates chronic
inflammatory diseases, such as asthma and inflammatory bowel disease. In transplantation,
the survival of organs transplanted into obese patients is reduced compared with allografts
in lean recipients. However, whether this is due to increased alloimmunity remains to be
addressed conclusively. Methods We used a mouse model of high-fat diet (HFD)–induced
obesity and assessed immune responses to allogeneic stimulation in vitro, allogeneic …
Background
Obesity promotes a state of low-grade inflammation that exacerbates chronic inflammatory diseases, such as asthma and inflammatory bowel disease. In transplantation, the survival of organs transplanted into obese patients is reduced compared with allografts in lean recipients. However, whether this is due to increased alloimmunity remains to be addressed conclusively.
Methods
We used a mouse model of high-fat diet (HFD)–induced obesity and assessed immune responses to allogeneic stimulation in vitro, allogeneic splenocyte immunization in vivo, and allogeneic heart transplantation.
Results
Our results indicate that HFD altered the composition and phenotype of splenic antigen-presenting cells that led to their enhanced capacity to stimulate T cells. Immunization with allogeneic splenocytes in vivo resulted in increased alloreactivity, as determined by IFNγ production. Moreover, cardiac allograft rejection in HFD mice was modestly accelerated compared to aged-matched control animals fed a low-fat diet, correlating with enhanced alloreactive T cell function.
Conclusions
Our results highlight the increased alloresponse triggered by HFD-induced obesity and its negative impact on transplant outcome.
Lippincott Williams & Wilkins