High Fat Diet Contributes to Organ Rejection After Transplant

Hyperlipidemia found to alter immune response.

Specialty pharmacists counseling patients following an organ transplant should keep a close eye on the eating habits of these individuals.

A pair of studies recently published online in the American Journal of Transplantation found that hyperlipidemia speeds up the rejection of transplanted hearts in mice. Utilizing models that imitate health conditions found in human transplant patients, researchers determined that transplant rejection was accelerated regardless of whether hyperlipidemia was attributed to genetics or specifically to a high fat diet.

"Our work fundamentally changes how we view transplant rejection,” senior author John Iacomini, PhD, said in a press release. “The common cause of transplant rejection in these mice was a high fat diet. We also demonstrate that the canonical understanding of organ rejection is not complete.”

In mice with hyperlipidemia caused by a genetic mutation of apolipoprotein E (ApoE) that received a high fat diet equivalent of fried food in humans, the transplanted heart was rejected after 21 days. Healthy mice with hyperlipidemia caused by receiving a high fat diet had their transplanted hearts last 51 days.

Meanwhile, mice with hyperlipidemia caused by a genetic mutation of ApoE who were fed a lower fat diet had their transplanted hearts last 61 days and healthy mice fed a lower fat diet had transplanted hearts that lasted more than 100 days.

"We used mice with conditions that mimic those often found in transplant patients -- hyperlipidemia is common in patients before transplantation but can also be caused by drugs to prevent organ rejection -- and discovered that it accelerates organ rejection,” co-first author, Jin Yuan, MD, PhD said in a press release. “The main problem for patients is rejection, so if organ rejection can be controlled, survival increases.”

The researchers noted that studies of organ transplant outcomes need to examine the overall health of the recipient.

"Most of our understanding of transplant rejection comes from work done over the past 50 years using healthy animal models,” co-first author Jessamyn Bagley, PhD, said in a press release. “It led us to believe that transplant rejection is caused by a type of T helper cell called Th1. This is the canonical understanding of organ rejection. We found, however, that increased levels of another type of T helper cell, known as Th17, are partially responsible for accelerated heart-transplant rejection in mice with hyperlipidemia. Hyperlipidemia also affects regulatory T cells and disrupts their ability to prevent transplant rejection.”