Protein controls fat metabolism

March 17, 2020

Many foods - whether it's the mozzarella on your favorite pizza, the olive oil in salad dressing or hollandaise sauce during asparagus season - contain lots of fat. The fatty acids in these foods are among the essential nutrients that people need to survive. When someone eats more fatty acids than the body can immediately convert into energy, the extra amount is stored in tissues - often in the form of unwanted rolls of fat around the hips or stomach - and serves as a kind of reserve supply.

The quantity of fatty acids transported by blood to the tissues and deposited there is determined by a wide range of factors. Researchers at the Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC) have now identified one of these factors as the protein EHD2.

If this protein is missing completely, fat-storing cells take up significantly more fatty acids from the cellular environment. Dr. Claudia Matthaeus first observed this phenomenon in the brown adipose tissue of mice during her work at the MDC. She finds it particularly exciting that EHD2 apparently plays a key role in human fat metabolism, too. "We have discovered that overweight people produce less EHD2 than people with normal weight," Matthaeus says. It is not clear yet why this is the case. Based on these new insights, Matthaeus and her colleagues, including researchers from the MDC research group led by Professor Oliver Daumke, assume that EHD2 controls a metabolic pathway that regulates fatty acid uptake in fat cells. This pathway is modified in obesity, the researchers write in the journal PNAS.

Cellular uptake of fat occurs when portions of the cell membrane pinch off

Oliver Daumke is long acquainted with EHD2. The structural biologist has been characterizing the structure and mechanimsm of this protein for more than ten years. As a membrane protein, EHD2 resides inside muscle and fat cells. During the inward folding of the cell envelope, small flask-shaped membrane structures called caveolae are formed. These invaginations either remain on the surface of the cell membrane or they pinch off and carry foreign material - such as fatty acids - into the cell. This process is known as endocytosis, Daumke explains. The researcher assumes that the EHD2 protein assembles into ring-like structures around the neck of the membrane vessel and thus stymies the pinch-off process. Daumke is convinced that if EHD2 is not present as a stabilizer, caveolae pinch off more frequently and the cell takes up more fat.

This is precisely what Matthaeus and her colleagues examined. The researchers worked with mice in which the EHD2 gene had been switched off. Using an electron microscope, Matthaeus observed that compared to normal mice, many more caveolae had become detached from the plasma membrane. She was also able to determine that fatty acid uptake was greater in cells lacking EHD2 and that the lipid droplets, which are intracellular accumulations of fat, were larger in these cells.

Obesity influences EHD2 production

Matthaeus asked herself if she would also be able to observe an influence of EHD2 on fat metabolism in humans. So she, together with a colleague from Leipzig University, studied tissue samples from men and women with different body weight. She quickly discovered that in people who were overweight (body mass index of 25 or higher), cells produce less EHD2 than in slim people. The researcher presumes that there is a correlation between frequent membrane pinch-off and the formation of fat depots. "During obesity, we observed that the number of caveolae and their detachment from the membrane get out of sync," Matthaeus says.

In November, Matthaeus left the MDC to take a position at the National Institutes of Health in the United States. There she plans to continue her research into caveolae and fat metabolism. "There are still many unanswered questions," Matthaeus says. She is now especially interested in investigating the transport of fatty acids within the cell and the formation of lipid droplets.

Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Related Overweight Articles from Brightsurf:

Overweight and obesity are associated with a low sperm quality
Researchers from the Rovira i Virgili University in collaboration with researchers from the University of Utah have carried out a systematic review and meta-analysis evaluating the association between adiposity (normal weight, overweight, obesity, and low weight) and the sperm quality.

Depression in adults who are overweight or obese
In an analysis of primary care records of 519,513 UK adults who were overweight or obese between 2000-2016 and followed up until 2019, the incidence of new cases of depression was 92 per 10,000 people per year.

Overweight from cosmetics
Parabens are used as preservatives in cosmetics. If pregnant women use cosmetics containing parabens that remain on the skin for protracted periods, this may have consequences for their child's subsequent weight development.

Overweight before age 40 increases the cancer risk
The risk of cancer increases considerably if you gain weight before the age of 40.

Overweight Danes are more likely to have overweight dogs according to new research
A new study from the University of Copenhagen reports that the prevalence of overweight dogs is markedly larger among overweight owners than among normal weight owners.

Overweight kids actually eat less right after stressful events
People often react to stress by binging on sweets or fattening comfort foods, cravings fueled by the appetite-stimulating stress hormone cortisol.

Abundant screen time linked with overweight among children
A recently completed study indicates that Finnish children who spend a lot of time in front of screens have a heightened risk for overweight and abdominal obesity, regardless of the extent of their physical activity.

Overweight, obesity in children across Europe
This study (called a systematic review and meta-analysis) combined the results of 103 studies with nearly 478,000 children (ages 2 to 13) to look at how common overweight and obesity are among children across Europe.

Overweight men are inhibiting childbirth
About 15% of couples in fertile age have experienced fertility problems.

Being overweight as a teen may be associated with cardiomyopathy in adulthood
The risk of developing cardiomyopathy, which often leads to heart failure, increased in adult Swedish men who were even mildly overweight around age 18.

Read More: Overweight News and Overweight Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to