Chronic stress may stimulate production of a protein that then goes on to block an enzyme that breaks down body fat, new evidence suggests.

Its role in stress brings new attention to the protein, called betatrophin, which was once hailed by researchers as a breakthrough therapy for diabetes, but later deemed ineffective.

While the latest properties of betatrophin have yet to be tested in clinical trials, researchers say the findings have potential implications for humans.

“Betatrophin reduces the body’s ability to break down fat, underscoring a link between chronic stress and weight gain,”

says Li-Jun Yang, professor of pathology, immunology, and laboratory medicine at the University of Florida.

Stress, Betatrophin, and Fat Metabolism

In the present study, mouse models experiencing metabolic stress produced significantly more betatrophin, and their normal fat-burning processes slowed down markedly. Such observations are significant because they shed new light on the biological mechanisms linking stress, betatrophin, and fat metabolism, Yang says.

Betatrophin set the scientific world abuzz in 2013, when a Harvard University study suggested it could increase the number of insulin-producing beta cells in people with diabetes—but later studies concluded that it had no such effect.

Now it seems that betatrophin has an important, if less celebrated, role: The results provide experimental evidence that stress makes it harder to break down body fat.

As reported in the study, betatrophin leads to less fat burning because it suppresses adipose triglyceride lipase, an enzyme that breaks down stored fat.

Experiments on cells derived from mice and humans were first used to establish betatrophin’s role in body fat regulation, Yang says. Next, researchers studied how betatrophin levels increased as mouse models experienced environmental and metabolic stress.

Both types of stress boosted betatrophin production in fat tissue and the liver. That finding established betatrophin is a stress-related protein.

While researchers have yet to test betatrophin’s effect on fat metabolism in humans, the new findings offer another reason why reducing stress can be beneficial: While short-term mild stress can help people perform better and get through difficult situations, long-term stress can be far more detrimental.

“Stress causes you to accumulate more fat, or at least slows down fat metabolism. This is yet another reason why it’s best to resolve stressful situations and to pursue a balanced life,” Yang says.

Yuan Zhang, et al. Angiopoietin-like protein 8 (betatrophin) is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids Volume 1861, Issue 2, February 2016, Pages 130–137

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