How Cell Death Occurs From Fat and Sugar Overload

How Cell Death Occurs From

Fat and Sugar Overload

Excess fat and sugar don't just cause people to gain excess weight and unwanted inches, but cause metabolic stress and can push some cells in the body to commit suicide. These cells don't have the ability to tolerate the toxic environment excess fat and sugar cause, and ultimately initiate their own death.

Research scientists at Washington University School of Medicine in St. Louis have recently discovered three unexpected culprits that help a cell overloaded with fat commit suicide. They've demonstrated that these molecules leading a cell to self-destruct are small strands of RNA, not proteins, as previously theorized..Since these small nucleolar RNAs play well-known roles in building proteins, the researchers were surprised to discover them killing cells.

The research has been published in Cell Metabolism,
and is the first study to link these small RNA molecules to the
cellular damage characteristic of common metabolic diseases like diabetes."When these three RNAs are present, the cells die in response to metabolic stress, such as exposure to large amounts of fats," says cardiologist Jean E. Schaffer, MD, the Virginia Minnich Distinguished Professor of Medicine at Washington University. "But if these three RNAs are missing, the cells don't die."

It's important to recognize that cell suicide is a natural process that protects healthy tissues from damaged cells, but the process can sometimes fall out of balance. For example,
if the cell death pathway gets shut down, damaged cells may divide and lead to cancer.

Conversely, too much cell death due to abnormal metabolites, such as high levels of fats and sugar, can impair the function of tissues in the body. This type of excess cell death is involved with diabetes complications such as heart failure. It is important to understand how abnormal metabolites cause cells to die, it will be helpful in the search for effective new therapies.

According to Dr.Schaffer, who is also the director of the Diabetic Cardiovascular Disease Center and Diabetes Research Training Center at the School of Medicine, the fact that small RNA molecules are involved in this cell death pathway is totally unexpected.

"When we set out to find genes causing cellular damage due to excess fat, we were expecting to find genes that code for proteins," she explains. "Instead, we identified an entirely new function for three small nucleolar RNAs. Unrelated to their well-defined role in the cell's protein-making machinery, we discovered they participate in how cells go on to die from overload of nutrients."

In a classic genetics experiment, the researchers initially identified a genetic region that, when disabled, allows cells to continue living in high fat and high sugar conditions. While the region codes for a protein, they demonstrated that the protein itself is not involved in initiating cell death.

"At first this result really puzzled us," Dr. Schaffer continued. "The mutation occurs in a region that encodes a protein, as we might expect. But returning the protein to the mutated cells did not return the cell death response." The three small nucleolar RNAs function together not only to promote cell death from nutrient excess, but also to promote more general mechanisms of cell death in diseased tissues.

Dr. Schaffer is a cardiologist who treats patients at Barnes-Jewish Hospital; She ephasizes how a multifaceted approach is necessary to manage the complexities of metabolic diseases like diabetes and obesity. Encouraging patients to reduce the amount of fat and sugar in the diet is a key strategy for treatment.

However, when dietary modification becomes ineffective, it would be helpful to have other ways to reduce cellular damage from excess fats in the muscles, heart, pancreas, liver and other organs and the team continues to pursue the search for possible treatments. "That's where our future work is headed."

This research was supported by grants from the National Institutes of Health (NIH), the Burroughs Welcome Foundation, the Washington University Diabetes Research Training Center and the Washington University Metabolomics facility.

Story Source:
Washington University School of Medicine
Journal Reference:
Small nucleolar RNAs U32a, U33 and U35a are critical mediators of metabolic stress.
Cell Metabolism (July 2011)

This article is for informational and educational purposes only, and is not intended to provide medical advice, diagnosis or treatment. Consult with your doctor or healthcare professional for medical and nutrition advice.