Enzyme discovery could improve treatments for obesity, related diseases

Understanding the process by which fatty acids reassemble into triglycerides could lead to new ways to treat obesity.

Harvard University researchers have unraveled a metabolic process—and the enzyme responsible for it—that protects cells from harmful fats. The discovery could lead to improved treatments for obesity and its related diseases.

Triglycerides, a type of fat found in the human body, are broken down into fatty acids and then transported out of fat cells to other tissues in the body for energy. But unlike triglycerides, fatty acids can damage the endoplasmic reticulum, a cell component that makes cellular products, such as proteins and fats.

Through a process called re-esterification, any leftover fatty acids in the fat cells turn back into triglycerides. This protects the endoplasmic reticulum and wards off inflammation in body fat.

Looking at cell processes in mice and in human cells, the Harvard team found that the enzyme diacylglycerol acyltransferase (DGAT1) drives re-esterification. It behaves like a “cellular police officer” to guard the endoplasmic reticulum from fatty acids, researchers said in a statement. Until now, it was unknown why some triglycerides, after being broken down into acids, reassemble themselves. The research is published in Cell Metabolism.

"To better understand what happens when cells are overwhelmed with fat during obesity, we first have to understand how the system normally deals with fluctuations in lipids," said Tobias Walther, professor of genetics and complex diseases at Harvard University’s Chan School of Public Health and co-senior author of the study, in the statement. "Our findings will hopefully spark new ideas on how to prevent the health consequences of obesity."

Obesity may be treated with pharmaceuticals, which can suppress appetite or reduce fat absorption, or medical devices, such as weight-loss balloons that take up space in the stomach to prevent overeating.

A variety of new approaches are being studied, such as using an approved Alzheimer’s drug to reduce inflammation and treat symptoms of metabolic syndrome, a group of conditions linked to obesity and that increases a person’s risk of developing diabetes and heart disease. Another research group recently found that removing the enzyme O-GlcNAc transferase from mice caused them to overeat, a discovery that could help in the quest for new drugs that control appetite.