Fat. We love it in our foods but hate it in our bodies. What if I told you that our body makes a small molecule that can be harnessed to get rid of the fat we hate and improve blood sugar and heart health at the same time?

I am talking about bilirubin. Those who know of bilirubin are extremely cautious of this molecule as it is usually associated with liver disease and jaundice (where the skin and eyes turn yellow). But bilirubin is a normal product of our body, created after our red blood cells die and release a molecule called heme.

Red blood cells in our blood stream have a life span of about 120 days, so turnover from our bone marrow is constant. Heme is eventually metabolized to molecules that are excreted and which contribute to the color of our urine and feces. Bilirubin is one of the metabolic products of this pathway within our body.

Interestingly, at only slightly elevated levels, bilirubin can serve as a protector against obesity, diabetes, and heart disease. Elevated bilirubin levels are also a characteristic of people who have Gilbert’s Syndrome, which is a mild genetic disorder resulting in slightly elevated bilirubin in the blood, although these people generally have no jaundice or liver problems.

It is important to investigate this phenomenon as it could reveal an all-in-one anti-obesity, anti-diabetic, and heart-protective drug. Our research is focused on exploring how this yellow-inducing molecule may be a key to addressing the obesity epidemic in America.

Our lab investigates how bilirubin binds with a protein called Peroxisome Proliferator-Activated Receptor-alpha (PPARα) in cells to induce healthy changes. Bilirubin is not the only molecule to bind to PPARα and induce its activities. Drugs such as fibrates (fenofibrate) have been used clinically to help reduce fats, also called lipids, in the blood. Unfortunately, fibrates have limited use and can only decrease lipids in the blood.

Bilirubin, on the other hand, has been shown to reduce lipids, regulate blood sugar, and improved heart health in mouse models and in man. Work in our research lab has demonstrated that these beneficial effects are due to bilirubin after binding with PPARα to cause all of the beneficial changes we have seen in human populations.

We have demonstrated that when PPARα is reduced in liver cells that the beneficial effects of bilirubin are reduced by 95 percent. This lets us know that PPARα is indeed necessary for bilirubin-induced changes in liver cells. Likewise, in liver and kidney cells that lack the ability to create bilirubin, there is a significant decrease in the ability of these cells to get rid of lipids, which then leads to increased cell death. Our lab also has shown that PPARα is necessary to cause the bilirubin-induced improvement in blood sugar regulation as well as weight loss in a mouse model.

Further research is needed to understand the effects of bilirubin as a beneficial drug, such as understanding mechanisms of how bilirubin bound to PPARα actually controls lipid and blood sugar in mouse models. This information also will be important to help reveal any side effects that may impact humans. To date, no harmful side effects have been reported. Further studies also will include clinical studies using synthetic bilirubin-like molecules within the human body.

Bilirubin has come a long way from a molecule indicating disease to being a potential therapy. This exciting research is opening new doors towards understanding how naturally occurring molecules can be harnessed to combat our current epidemic of obesity-related health issues.

Darren Gordon is an MD/PhD student in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program in the Molecular Medicine track. Darren is doing his research in the laboratory of Terry Hinds, PhD. For more information, contact Darren.Gordon@rockets.utoledo.edu or go to utoledo.edu/​med/​grad/​biomedical.

First Published October 6, 2019, 12:00 p.m.