Researchers discover a new gene involved in obesity

June 20, 2013

The discovery of an unexpected function for a gene that was associated to another process in the organism might be a solution in search of a problem, a clue to unsuspected connections. That is what has happened with RAP1, a gene that protects telomeres— the ends of chromosomes—after researchers from the Spanish National Cancer Research Centre (CNIO) surprisingly discovered its key role in obesity.

"We still don't know what to attach to it, but it is at the very least interesting that a telomere gene is related to ", says Maria Blasco, CNIO director and co-author of the study published today in the journal Cell Reports.

RAP1 forms part of the shelterin complex, a group of proteins that make up the protective hood of —the DNA sequence at the ends of that shortens with each and thus measures the ageing of the organism. There are six shelterins, and CNIO's Telomeres & Telomerase Group, which studies them in-depth, has discovered that RAP1, contrary to the rest, is not essential for the survival of the organism; but that does not mean RAP1 is not important. The reverse is rather the case: when comparing the genomes of different species, it can be observed that RAP1 is the most conserved shelterin of all. Despite the long history of evolutionary changes, RAP1 has not changed; it is present even in yeast. This normally implies an important role in the organism, but which one?

CNIO researchers had discovered that RAP1, in addition to being located in telomeres, is also present in the rest of the chromosome; they supposed it acts regulating the action of other genes. In order to analyse this other potential function, and its importance in the organism, CNIO researchers created a lineage of mice without RAP1 and, to their surprise, discovered a model for obesity.

MICE LACKING RAP1 GAIN MORE WEIGHT

"Mice—especially female mice—without RAP1 do not eat more, but do gain weight. They suffer from metabolic syndrome, accumulate abdominal fat and present high glucose and cholesterol levels, amongst other symptoms", says Paula Martínez, first-author of the study.

The reason is that RAP1 plays an important role in the regulation of genes involved in metabolism. In particular, researchers have discovered that it acts on the same signalling pathway mediated by another protein: PPAR- gamma (PPAR-γ). In fact, PPAR-γ deficient mice suffer from a type of obesity "surprisingly similar" to that seen in mice without RAP1.

The next step in the research will be to study if RAP1 also plays a role in human obesity. "This discovery adds an element to the obesity equation, and opens up a possible new link between metabolic dysfunction and ageing, via a present in telomeres", says Blasco.

Explore further: Psychiatric disorders linked to a protein involved in the formation of long-term memories

More information: RAP1 Protects from Obesity through Its Extratelomeric Role Regulating Gene Expression. Paula Martínez, Gonzalo Gómez-López, Fernando García, Evi Mercken, Sarah Mitchell, Juana M. Flores, Rafael de Cabo, Maria A. Blasco. Cell Reports (2013). doi: 10.1016/j.celrep.2013.05.030

Related Stories

Psychiatric disorders linked to a protein involved in the formation of long-term memories

June 17, 2013
Researchers have discovered a pathway by which the brain controls a molecule critical to forming long-term memories and connected with bipolar disorder and schizophrenia.

Researchers identify a new gene that is essential for nuclear reprogramming

June 5, 2013
Researchers are still fascinated by the idea of the possibility of reprogramming the cells of any tissue, turning them into cells with the capacity to differentiate into cells of a completely different type— pluripotent ...

Caloric restriction has a protective effect on chromosomes

January 23, 2013
One of the indicators of a cell's health is the state of its DNA and containers—the chromosomes—so when these fuse together or suffer anomalies, they can become the source of illnesses like cancer and/or ageing processes.

Rap1 plays role in smooth muscle cell vasoconstriction

August 6, 2012
(HealthDay) -- The Ras-related small GTPase, Rap1, couples to RhoA, and is involved in relocalization of G protein-coupled α2C-adrenoceptors (α2CARs) in smooth muscle cells derived from human dermal arterioles (microVSM), ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly identified genetic marker may help detect high-risk flu patients

July 17, 2017
Researchers have discovered an inherited genetic variation that may help identify patients at elevated risk for severe, potentially fatal influenza infections. The scientists have also linked the gene variant to a mechanism ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.