Complain about a product or service

Protein Triggers Fat-Saturated Cell Death

January 31, 2006

Diabetes • Studies Find Link Between Diabetes and Alzheimer's • Avandia Maker Failed To Report Required Data • Prediabetes: What You Should Know • Study: Large-Breasted Women More Diabetes-Prone • U.S. Diet Dishes Up Diabetes • Weight-Loss Surgery Seen Beneficial to Diabetics • Lack of Deep Sleep May Increase Diabetes Risk • Study: Avandia May Do More Harm than Good • FDA Orders New Warning For Avandia • U.S. Kidney Disease on the Rise • Fish Oil May Fight Diabetes • Avandia vs. Actos: A Doctor's Advice • Avandia Linked to 42% Greater Risk of Heart Attack • Soft Drink Sweetener Linked to Diabetes in Kids • Diabetes Drugs to Get 'Black Box' Warnings • FDA Rejects Advice to Pull Avandia From Market • FDA Advised to Pull Avandia From Market • Avandia, Other Diabetes Drugs Increase Risk of Heart Failure • Dairy Products May Protect Against Metabolic Syndrome • Portion-Control Dishes May Help Obese Diabetics • FDA Issues Safety Alert on Diabetes Drug Avandia • Stem Cell Treatment May "Cure" Diabetes • Diabetes Risk May Be In The Genes • Holiday Gluttony Can Spell Disaster for Undiagnosed Diabetics • Malaria Drug May Fight Common Cause of Diabetes, Heart Disease • Feds Attack Fake Diabetes Cures • FDA Approves New Treatment for Diabetes • Feds Warn Of Counterfeit Diabetes Tests • Study: Weightlifting Helps Overweight Teens Avoid Diabetes • Researchers Say They Can Reverse Type 1 Diabetes • Study: Obesity Major Factor in Diabetes Epidemic • Too Much, Too Little Sleep Linked To Diabetes In Men • Procedure Cures Some Diabetic Mice • Ethnicity Skews Diabetes' Effect on Heart • Pig Cells May Be Useful in Diabetes Treatment • Protein Triggers Fat-Saturated Cell Death • FDA Approves Diabetes Inhaler Exubera • FDA Panel Greenlights Diabetes Inhaler • Breastfeeding May Decrease Diabetes Risk • Low-Fat Dairy Products May Lower Diabetes Risk in Men • Scientists Find Diabetes "Switch" • New Diabetes Treatment Approved • Knowledge of Diabetes Doesn't Always Affect Outcomes • Moderate Exercise Helpful to Diabetes-Prone Women • Life Expectancy Increases; Diabetes Epidemic Worsens

Investigating the harmful health effects of excess fat, researchers at Washington University School of Medicine in St. Louis have identified a protein that triggers death in mammalian cells overloaded with saturated fat.

When the researchers halted production of this protein, called EF1A-1, the cells were able to thrive in ordinarily damaging amounts of the saturated fat palmitate, a fat abundant in Western diets.

At the same concentration of palmitate, normal cells still producing EF1A-1 rapidly died. The study will be published in the February 2006 issue of Molecular Biology of the Cell.

"When lipids (fats) accumulate in tissues other than adipose tissue, cellular dysfunction or cell death results," says senior author Jean Schaffer, M.D., associate professor of medicine and of molecular biology and pharmacology.

"For example, preliminary studies on animals suggest that the accumulation of fat in the pancreas contributes to the development of diabetes, and accumulation of lipids in skeletal muscle of leads to insulin resistance."

Other studies have linked the genesis of heart failure to fat-induced cell dysfunction and cell death in the heart.

"As physicians our primary focus in diabetic patients is on glucose control," says Schaffer, a member of the Center for Cardiovascular Research at the School of Medicine and a cardiologist at Barnes-Jewish Hospital. "But it appears we should also be more aggressive with respect to lowering lipids such as triglycerides and fatty acids."

With the discovery of EF1A-1's role, this study is the first to identify a critical step in the pathway that leads from high cellular fat to cell death, according to Schaffer. EF1A-1 is an extremely abundant protein with several diverse functions within cells, including protein synthesis and maintenance of the cytoskeleton, the cell's internal support structure.

In mammalian cells grown in culture, the researchers saw that EF1A-1 and the fat palmitate work hand in hand: the presence of EF1A-1 dictated sensitivity to palmitate-induced cell death, and palmitate caused a rapid increase of the amount of EF1A-1 produced.

Schaffer's laboratory earlier had developed a transgenic mouse that accumulates fat in its heart muscle cells resulting in the death of cells, heart failure and premature death. They found that EF1A-1 was increased nearly three-fold in the hearts of these animals.

Removal of EF1A-1 protected cells from palmitate-induced death, and its absence allowed cells to withstand assault by highly reactive oxygen molecules. According to study authors, this indicates that EF1A-1 probably contributes to cell death from oxidative stress, which is known to stem from high lipid levels.

Cytoskeletal changes seen in cells missing EF1A-1 suggested to the researchers that EF1A-1's cytoskeletal role also is important in cell death resulting from fat overload.

"Cells have a lot of mechanisms for incorporating fatty acids into storage forms, for metabolizing them or for using them in cellular membranes," Schaffer says. "But saturated fats like palmitate are poorly stored in the tiny fat droplets normally found in most cells and therefore are more likely to enter into pathways that lead to cell death such as the one in which EF1A-1 is involved."

In the process of identifying the role of EF1A-1, the lab members uncovered other proteins implicated in the toxicity of excess fats. They are now investigating each to find out what part it plays.

Future investigations by Schaffer's research team will study the EF1A-1 protein to see whether fatty molecules directly alter the protein, or if they cause it to relocate within the cell.

Report Your Experience
If you've had a bad experience -- or a good one -- with a consumer product or service, we'd like to hear about it. All complaints are reviewed by class action attorneys and are considered for publication on our site. Knowledge is power! Help spread the word. File your consumer report now.

Back to the top |