Researchers discover pathway that decreases fat absorption _ the michigan daily

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Removing a protein from the liver may help reduce cholesterol in the blood, according to a new study conducted by researchers in the University’s Life Sciences Institute.

Using mice as subjects for the study, researchers found a pathway that contributes to cholesterol absorption. Ultimately, high cholesterol absorption can lead to serious medical issues including hyperlipidemia, a condition associated


with abnormally high amounts of lipids, or fats, in the blood, and atherosclerosis, a disease associated with cholesterol buildup in arteries, which forms plaque, clogging the arteries.

Jiandie Lin, senior author of the study and associate professor of cell and developmental biology, elaborated on the dangers of atherosclerosis, saying plaque in the arteries can move through the body and cause other conditions, including heart attack and stroke.

Lin said he and his colleagues tried to understand how blood cholesterol concentrations are regulated in the body by comparing healthy mice to those with diseases. The team started by looking at a particular pathway of proteins called BAF60 proteins in the mice. BAF60 proteins are present in fat tissue, skeletal muscles and the liver. In the liver, the protein is labeled BAF60a.

Compared to other sites, the liver contains elevated levels of the protein. Lin and the research team were curious whether the increased amount of this protein was contributing to hyperlipidemia.

When fed a diet consisting of foods high in fat and sugar, the mice developed hyperlipidemia.

“Because we know that this western diet increased blood lipids, and we know that this Western diet also increased the level of this protein in the liver … the question was really whether this increase in protein level somehow contributes to hyperlipidemia,” Lin said.

The mice that did not have the protein did not develop the same cholesterol issues as mice that had the protein.

After this discovery, Lin said the team wondered why this particular protein, when removed from the liver, could actually protect the mice from high blood lipids.

According to Lin, bile — a fluid that aids digestion — is made in the liver and then gets released into the small intestine to absorb lipids and cholesterol. Lin said that because the protein helps regulate bile, it ultimately aids with the absorption of cholesterol, too. Without the protein, less bile is created, and in turn, less cholesterol is absorbed by the intestines, resulting in less of a risk for cholesterol-related diseases.

Lin said it is unclear whether this pathway in the mouse is regulated the same way in humans, though it is feasible that there is a way to similarly block cholesterol absorption.

Zhuo-Xian Meng, lead author of the study and a research investigator at the University, said current treatments for cholesterol-based diseases in humans do not work for everyone.

“We know that current treatment can only be efficient for about 70 percent of patients,” Meng said.

Therefore, he said researching these pathways could lead to the development of new treatments for the hyperlipidemia and atherosclerosis.

Meng said, from an evolutionary perspective, the pathway in the liver that absorbed high-cholesterol foods was beneficial during a time when an abundance of food was not as common. In other words, the pathway used to be important for human survival.

“We always eat a lot, and in this case, it’s no longer beneficial,” Meng said. “People no longer worry about being hungry.”