Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Fat overload kills mammalian cells — key culprit identified


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.

The internal "skeleton" (in red) of cells is altered by exposure to high 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.

Borradaile NM, Buhman KK, Listenberger LL, Magee CJ, Morimoto ETA, Ory DS, Schaffer JE. A critical role for eukaryotic elongation factor 1A-1 in lipotoxic cell death. Molecular Biology of the Cell, February 2006.

Funding from the National Institutes of Health, the Washington University School of Medicine--Pharmacia Biomedical Program (JES) and the Heart and Stroke Foundation of Canada supported this research.

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Gwen Ericson | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences

nachricht Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>