Tiny fat-burning molecule may help fight obesity

Scientists have identified a molecule that may help combat the global epidemic of obesity by preventing excessive weight gain in cases where diets or exercise have no effect.
When the molecule was fed to obese mice, the animal's metabolism sped up and their excess weight was shed.
It is doing so by recruiting the help of a body's own genes in countering the effects of a high-fat diet.
A high-fat diet may contribute to obesity in some individuals. Treatment in such situations has focused on behavioural changes, which is highly challenging to achieve for the general population on a long term basis.

Researchers from a French biotechnology company ABIVAX introduced the concept of recruiting the help of our genes in countering the effects of a high-fat diet, instead of focusing on reducing the intake of high-fat food.
They know that the structure of some genes that help to produce certain proteins can actually change when someone constantly eats too much high-fat food.

In the process, the person can become overweight or obese, or develop other lifestyle-related metabolic disorders such as diabetes or heart problems.
In many cases, the same gene can produce two or more alternate proteins, based on how the translation from DNA (gene) to proteins is processed.

One of these genes is LMNA, which plays a role in the development of different metabolic disorders.
The LMNA RNA, which is the genetic material resulting from a process called DNA transcription, is modified by three SR proteins called SRSFI, SRSF5 and SRSF6.
In this process called splicing, the genetic material encoded in the RNA is basically diced or shifted around and therefore alters the resulting proteins.
Researchers found that a small molecule is able to change the way one particular SR protein, SRSFI, works in the bodies of mice that gained excessive weight after being fed a high-fat diet.

SRSFI determines which of the gene products of opposing effects could be produced from a single LMNA gene. One gene product promotes fat storage, the other opposes it.
This study showed that blocking SRSFI with a compound promotes gene expression of the protein that burns calories and prevents fat gain or induces fat loss when mice are on a high-fat diet. It did not have any effect on lean mice of normal weight.
This approach alters the animal's metabolic rate or energy expenditure. It means that it can speed up the metabolism of obese animals, and that their bodies start to function at a higher energy level shedding the excess weight.

In the process, their bodies started to burn through much more fat, as especially fatty acids serve as much-needed sources of energy.
The study was published in the International Journal of Obesity.