Gladstone scientists reveal the genetics of fat storage in cells

May 21, 2008

New research by the Gladstone Institutes of Cardiovascular Disease (GICD) and the University of California, San Francisco (UCSF), has revealed the genetic determinants of fat storage in cells, which may lead to a new understanding of and potential treatments for obesity, diabetes, and heart disease. While scientists have long understood that lipid droplets contribute to fat build up in cells, the genes involved in droplet biology have been a focus of extensive research.

In a study published in Nature, scientists in the laboratories of Drs. Robert V. Farese, Jr., of Gladstone and UCSF, and Peter Walter, of UCSF, devised a genetic screen to identify genes responsible for fat storage in cell of fruit flies, and potentially other species.

“For some time, we have been studying the enzymes that make fats,” said Dr. Farese, senior investigator. “But clearly, we need to know a lot more about the most basic processes that regulate cellular fat storage to be able to make progress on some very serious human diseases.”

To identify novel genes involved in fat storage, GICD scientist Dr. Yi Guo, and Dr. Tobias Walter, formerly of Dr. Walter’s laboratory and now of the Max Planck Institute of Biochemistry in Germany, initiated a major discovery project, in which they used RNAi screens to individually inactivate all the genes in cells from fruit flies. Basic cellular processes in humans are highly conserved in cells from fruit flies, so the results should mostly be applicable to human biology. Drs. Guo and Walther completed the initial survey and have now begun to study in detail the genes that have the most striking effects on fat storage in cells.

Surprisingly, they found that ~1.5% of all genes function in lipid-droplet formation and regulation. These genes proved to be determinants of the size and number of lipid droplets in cells. Several of these genes were investigated in detail and shown to profoundly affect droplet morphology and lipid utilization. When the individual genes were deleted, the resulting cells could be separated into five distinct phenotypic classes, based on the number and appearance of the lipid droplets.

The most interesting genes will be advanced into functional studies in flies and mice. These new studies promise two major outcomes: significant advances in understanding the processes that regulate fat metabolism in cells and novel therapeutic targets for treating diseases, such as obesity and diabetes. Additionally, the findings have implications for engineering plants and microorganisms to maximize seed oil production and biofuels, respectively.

“With this screen completed, the work turns now to many fascinating questions,” said Dr. Guo. “How are lipid droplets formed" What regulates their size, numbers, and cellular locations" Do they help to traffic lipids within the cell" How does this cell biology relate to physiology and disease" These are early days in this area of biology, and the field is wide open.”

Source: Gladstone Institutes

Explore further: Assortativity signatures of transcription factor networks contribute to robustness

add to favorites email to friend print save as pdf

Related Stories

FIXD tells car drivers via smartphone what is wrong

11 hours ago

A key source of anxiety while driving solo, when even a bothersome back-seat driver's comments would have made you listen: the "check engine" light is on but you do not feel, smell or see anything wrong. ...

Team pioneers strategy for creating new materials

12 hours ago

Making something new is never easy. Scientists constantly theorize about new materials, but when the material is manufactured it doesn't always work as expected. To create a new strategy for designing materials, ...

Shell files new plan to drill in Arctic

12 hours ago

Royal Dutch Shell has submitted a new plan for drilling in the Arctic offshore Alaska, more than one year after halting its program following several embarrassing mishaps.

Aging Africa

13 hours ago

In the September issue of GSA Today, Paul Bierman of the University of Vermont–Burlington and colleagues present a cosmogenic view of erosion, relief generation, and the age of faulting in southernmost Africa ...

Recommended for you

Mutation disables innate immune system

18 hours ago

A Ludwig Maximilian University of Munich team has shown that defects in the JAGN1 gene inhibit the function of a specific type of white blood cells, and account for a rare congenital immune deficiency that ...

Study identifies genetic change in autism-related gene

Aug 28, 2014

A new study from Bradley Hospital has identified a genetic change in a recently identified autism-associated gene, which may provide further insight into the causes of autism. The study, now published online in the Journal of ...

NIH issues finalized policy on genomic data sharing

Aug 27, 2014

The National Institutes of Health has issued a final NIH Genomic Data Sharing (GDS) policy to promote data sharing as a way to speed the translation of data into knowledge, products and procedures that improve health while ...

The genes behind the guardians of the airways

Aug 27, 2014

Dysfunctions in cilia, tiny hair-like structures that protrude from the surface of cells, are responsible for a number of human diseases. However the genes involved in making cilia have remained largely elusive. ...

User comments : 0