Bile acids fire up fat burning

January 16, 2018, Ecole Polytechnique Federale de Lausanne

Obesity arises from an imbalance between energy intake and energy expenditure. As a result, current treatments try to decrease calorie intake and/or increase energy expenditure.

The problem is maintaining long-term effects. Non-invasive treatments, like diets and drugs that reduce intestinal ingestion are widely unpopular among patients, while bariatric surgery seems to be the only reliable treatment for obese people, despite being both expensive and invasive.

But now a new study led by the lab Kristina Schoonjans at EPFL, suggests that a specific group of could directly burn away the lipids in our fat depots, effectively making it a new therapy against obesity.

Bile acids are important constituents of bile, a yellow-green fluid produced in the liver that is stored in the gallbladder and secreted into the intestines during a meal. Bile emulsifies dietary fat into tiny globules that can be broken down by digestive enzymes to be absorbed by the intestine.

The EPFL scientists discovered that bile acids can turn fat-storing into fat-burning ones. This process is called thermogenesis (literally, "heat production") and it helps maintain body temperature in cold environments.

There are three different types of fat cells: white fat cells, which store ; , which expend energy; and the so-called "beige" fat cells, which are functionally related to brown cells while being located in typically white-fat depots.

Beige cells have recently attracted a lot of attention, especially because adults have very low numbers of active brown adipocytes that burn energy. But what can turn a white cell into a beige one - a process called "beiging" - and shift the balance from fat-storing to fat-burning?

The work of Schoonjans' team suggests that this process can be coordinated by secondary bile acids, metabolites that are generated by our liver and gut bacteria.

The study shows that activating the bile acid receptor TGR5 with molecules that mimic the action of bile acids (so called "mimetics") induces a remodeling of white fat cells into beige fat cells. The bile acids accumulate in the blood and interact with the TGR5 receptor on white fat cells to change their metabolic function.

This is more than a mere change of color, as the researchers also found that these bile acids increase the number of mitochondria in the new fat cells. This indicates higher energy consumption in the new, beige fat cells.

The bile-acid mimetics also triggered lipolysis, the first step in fat degradation, allowing the to use fatty acids as their main fuel source.

The study provides a direct connection between bile acids and fat loss and envisions novel therapeutic intervention in obese people. "We showed that bile acids are much more than a soap for digestion," says Kristina Schoonjans. "When their concentration in the blood reaches a certain level, it can turn up the thermostat and increase fat burning for energy and heat production".

"What is exciting about our discovery is that low concentrations of TGR5-selective molecules are sufficient to promote the beiging of white fat-storing cells, thereby bypassing the need to increase the total bile pool," says Laura Velazquez, first-author of the paper.

"Moreover, this study highlights mitochondrial fission —or the splitting of mitochondria— as a pivotal mechanism by which bile acids turn white fat into beige fat," adds Alessia Perino, co-first author. "It will be interesting to explore if mitochondrial fission is a universal mechanism for beiging in response to other stimuli".

Explore further: How bile acids could fight diabetes

More information: Laura A. Velazquez-Villegas et al, TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue, Nature Communications (2018). DOI: 10.1038/s41467-017-02068-0

Related Stories

How bile acids could fight diabetes

November 3, 2014
EPFL scientists have shown that a receptor activated by bile acids can reduce fat-tissue inflammation and insulin resistance in obesity-linked diabetes.

CD4 T cells, xenobiotic transporters, and metabolites in inflammatory bowel diseases

December 27, 2017
The immune system counters pathogenic microbes and toxins in the environment. The system comprises innate (non-specific) and adaptive (acquired) immunity. When innate immune cells recognize pathogens, the adaptive immune ...

Bile acid support the production of blood stem cells

January 29, 2016
A research group at Lund University in Sweden has been able to show that bile acid is transferred from the mother to the foetus via the placenta to enable the foetus to produce blood stem cells.

Gut microbiota regulates bile acid metabolism

April 19, 2012
A new study presented today at the International Liver Congress 2012 demonstrates that the gut microbiota has a profound systemic effect on bile acid metabolism.

Dysfunctional gene may be culprit in some Crohn's disease cases

December 19, 2017
This holiday season, millions of people will gather at airports ready to board planes for destinations around the world. Depending on the environment at their destination, their suitcases may be filled with sunscreen and ...

Cortisol controls recycling of bile acids

July 7, 2011
Nature sees to it that we do not have "too much choler" (bile) in our body. A delicately equilibrated regulation system ensures that there is always exactly the right amount of bile in the gallbladder. When we are hungry, ...

Recommended for you

Fabric imbued with optical fibers helps fight skin diseases

February 23, 2018
A team of researchers with Texinov Medical Textiles in France has announced that their PHOS-ISTOS system, called the Fluxmedicare, is on track to be made commercially available later this year. The system consists of a piece ...

Low-calorie diet enhances intestinal regeneration after injury

February 22, 2018
Dramatic calorie restriction, diets reduced by 40 percent of a normal calorie total, have long been known to extend health span, the duration of disease-free aging, in animal studies, and even to extend life span in most ...

Artificial intelligence quickly and accurately diagnoses eye diseases and pneumonia

February 22, 2018
Using artificial intelligence and machine learning techniques, researchers at Shiley Eye Institute at UC San Diego Health and University of California San Diego School of Medicine, with colleagues in China, Germany and Texas, ...

Gut microbes protect against sepsis—mouse study

February 22, 2018
Sepsis occurs when the body's response to the spread of bacteria or toxins to the bloodstream damages tissues and organs. The fight against sepsis could get a helping hand from a surprising source: gut bacteria. Researchers ...

Breakthrough could lead to better drugs to tackle diabetes and obesity

February 22, 2018
Breakthrough research at Monash University has shown how different areas of major diabetes and obesity drug targets can be 'activated', guiding future drug development and better treatment of diseases.

Fertility breakthrough: New research could extend egg health with age

February 22, 2018
Women have been told for years that if they don't have children before their mid-30s, they may not be able to. But a new study from Princeton University's Coleen Murphy has identified a drug that extends egg viability in ...

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.