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Researchers identify previously unknown link between stress and fat metabolism.

Metabolism is the process by which the human body converts caloric intake into energy. A number of factors determine the amount of calories burnt, namely caloric intake, physical activity, as well as, basic body functions such as breathing, circulating blood and cell regeneration. Stress can also affect the rate of the metabolism.  Stress responses include activation of the sympathetic nervous system and stimulation of epinephrine and cortisol release with these hormones potentially able to reduce insulin sensitivity over a long-period of time.  However, cortisol also triggers another set of responses in stressful situations, including suppressing immune system responses and slowing down digestive functions. If digestion is slowed, food may stay in the stomach too long which can cause ill health effects including intestinal blockage.

Mental stress has been shown to enhance catecholamine-mediated energy expenditure in obese patients and may lead to enhanced blood pressure responses and the absence of stimulation of glucose disposal in obese subjects during mental stress. It has been hypothesized that repeated professional or social stress may activate the sympathoadrenal system, resulting in high cortisol levels, stimulation of the sympathetic nervous system, and epinephrine secretion. All these factors may eventually lead to the development of obesity and insulin resistance.  However, it is still unclear as to how these many factors affect metabolism to cause these many conditions.  Now, a study from researchers at the University of Florida has shown that chronic stress stimulates production of betatrophin, a protein that then goes on to inhibit an enzyme involved in fat metabolism. The team state that its role as a stress-related protein brings new attention to betatrophin, which was once hailed by researchers elsewhere as a breakthrough therapy for diabetes, and later deemed ineffective.

Previous studies show that betatrophin is a liver-derived hormone that is associated with glucose homeostasis and lipid metabolism.  Recent studies show that betatrophin, also called angiopoietin-like protein 8 (ANGPTL8), acts together with ANGPTL3 to regulate lipid metabolism, glucose metabolism, and energy homeostasis.  Moreover, betatrophin promotes proliferation of pancreatic β-cells and induces insulin secretion.  It is known that betatrophin reduces the body’s ability to break down fat, underscoring a link between chronic stress, cortisol and weight gain.  However, its mechanism of action remains elusive.  The current study shows that betatrophin is a stress-related protein and that more betatrophin leads to less fat burning, because it suppresses adipose triglyceride lipase, an enzyme that breaks down stored fat.

The current study shows, in experiments on cells derived from mice and humans, betatrophin’s role in body fat regulation. The lab investigated how betatrophin levels increased as mouse models experienced environmental and metabolic stress. Results show that both types of stress boosted betatrophin production in fat tissue and the liver, which establishes betatrophin is a stress-related protein. Data findings show that the activation of ANGPTL8 gene transcription was mediated through the RAS/c-RAF/MAPK signaling pathway rather than the general GCN2/ATF4 pathways; specifically betatrophin activated the ERK signal transduction pathway in hepatocytes, adipocytes, and pancreatic β-cells, up-regulating early growth response transcription factor and down-regulating adipose triglyceride lipase.

Results show mouse models experiencing metabolic stress produced significantly more betatrophin, and their normal fat-burning processes slowed down markedly. The group state that such observations are significant because they shed new light on the biological mechanisms linking stress, betatrophin and fat metabolism.  They go on to add that their findings provide experimental evidence that stress makes it harder to break down body fat.

The team surmise that while the global medical community have yet to test betatrophin’s effect on fat metabolism in humans, their data helps to explain how reducing stress can be beneficial. For the future, the researchers state that while short-term mild stress can help people perform better and get through difficult situations, long-term stress can be far more detrimental. They go on to conclude that this is yet another reason why it’s best to resolve stressful situations and to pursue a balanced life.

Source: University of Florida Health


Angiopoietin-like Protein 8/Betatrophin in HepG2 Human Cell Line.  ©2016 R&D Systems, Inc. All Rights Reserved.
Angiopoietin-like Protein 8/Betatrophin in HepG2 Human Cell Line. ©2016 R&D Systems, Inc. All Rights Reserved.


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