In a new study, researchers have shed light on how a key fat-producing enzyme helps protect cells from a toxic form of fat. This new finding from the Harvard T.H. Chan School of Public Health and Howard Hughes Medical Institute contributes to a fuller, better understanding of the fundamental biology that underlies common metabolic diseases related to obesity, such as type 2 diabetes, fatty liver disease, and heart failure, and could lead to new insights on how to better treat such diseases.
“We are excited about these findings—they solve a mystery and show how fat synthesis protects cells from dysfunction and disease,” said Robert Farese, Jr., professor of genetics and complex diseases at Harvard Chan School.
Triglycerides are a type of body fat that 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.
The study published online in Cell Metabolism details how the researchers looked intowhat happens to triglycerides (a type of fat) in cells during lipolysis, the process through which the triglycerides are broken down into fatty acids and
transported for energy use to other tissues in the body. For decades, scientists have wondered why some triglycerides, after being broken down into fatty acids, wind up back in the cells in the form of triglycerides—a process known as “re-esterification.”And by examining cell processes both in mice and in human cells, the researchers found out why: Re-esterification helps protect a key cell organelle called the endoplasmic reticulum (ER). The ER helps make cellular products such as proteins and lipids and it can be damaged by fatty acids—but not by triglycerides. The researchers also found that an enzyme called DGAT1 (diacylglycerol acyltransferase) is crucial to the re-esterification process, acting as a sort of cell police officer to ensure that toxic fatty acids stay away from the ER.
“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.” He concluded.
