Weight Loss Hormone Activates Brain Pathways That Instruct Body To Burn Fat; Central Nervous System Key To Fighting Obesity Epidemic

Obesity
A hormone used in weight loss drugs is involved in the activation of a part of the brain that causes energy expenditure. Photo courtesy of Shutterstock

The hormone fibroblast growth factor 21 (FGF21) has been used in weight loss drugs due to its role as a novel metabolic regulator, but how the hormone functioned was unknown until now. New research suggests this hormone acts by activating a previously unknown activity in the central nervous system. The discovery, published in the journal Cell Metabolism, was made by UT Southwestern Medical Center obesity researchers.

FGF21 acts by affecting the energy balance in the body by causing the body to burn calories. UT Southwestern researchers have found FGF21 acts directly on the brain activating another hormone, called corticotropin-releasing factor (CRF). This hormone in turn stimulates the nervous system, activating brown adipose tissue — the main function of which is to generate energy from food.

"FGF21 is well known for playing a role in weight loss, and we had previously shown that the hormone can act directly on the brain in mice to influence functions like reproduction. In the new study, we show that FGF21 also acts directly on the brain to regulate obesity," said lead researcher Dr. Steven Kliewer in a statement.

The FGF21-CRF pathway activates one of the major divisions of the nervous system — the sympathetic nervous system. This division controls various homeostatic mechanisms in animals, and when activated by the FGF21-CRF pathway, signals brown fat to start burning. Brown fat is also called the “good fat” as it takes calories from normal fat and burns it, a process called "thermogenesis." Recent studies have also shown that it gets activated in cold and protects animals from it.

This study could help in developing drugs that target fat and help in weight loss in the obese. Obesity is the curse of modern times, with the Centers for Disease Control and Prevention estimating that it is now turning into an epidemic with more than 35 percent Americans obese.

Obesity increases the risk factor for developing serious conditions such as coronary heart disease, high blood pressure, type 2 diabetes, depression, and cancers. It also puts a significant burden on health care costs, with an annual expenditure of $147 billion being spent on obesity and related complications. Reduced productivity and chronic absence from work are other issues related to this condition.

Obesity is now the focus of several studies, says senior author Dr. David Mangelsdorf. "We have made great strides in understanding obesity in recent years," he said. "What this research shows is that the central nervous system must be considered when looking for weight loss treatments."

The researchers have dedicated their lives researching about the behavioral, metabolic, and cellular mechanisms that cause obesity. Their primary goal is to understand how the brain functions in regulating food intake and converting it into energy, and what goes wrong that results in obesity.

Source: Kliewer S, Mangelsdorf D, Owen B, Ding X, Colbert-Coate K, Bookout A. Cell Metabolism. 2014.

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