Discovery of primary body temperature regulator

EPAC1 boosts brown fat growth and beige adipogenesis.

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Brown fat cells turn energy into heat, helping eliminate extra fat and prevent heart problems. Scientists from University Hospital Bonn found a protein called EPAC1 that can be targeted with drugs to boost brown fat and make it more active. The goal is to develop medicines for weight loss. The study results are published in the respected journal ‘Nature Cell Biology.

Corresponding author Prof. Alexander Pfeifer, Director of the Institute of Pharmacology and Toxicology at the University Hospital Bonn and member of the Transdisciplinary Research Areas (TRA) “Life & Health” and “Sustainable Futures” at the University of Bonn, said “Obesity is defined as a pathological increase in white fat and has become a significant problem worldwide, with a significantly increased risk of cardiovascular diseases such as heart attack and stroke.”

“Exercise and dieting are not enough to effectively and permanently shed the pounds. Our energy-dense foods lead to energy being stored in white fat. But losing weight isn’t easy, as the body saves energy in response to a low-calorie diet. So our goal is to achieve additional energy release.”

The goal is to develop treatments that maintain a balanced energy level. Brown fat cells work like a natural heater, helping newborns handle cold after birth. However, adults have very little brown fat, primarily found in young and slender individuals. Researchers are exploring ways to increase brown fat while decreasing unhealthy white fat to address this.

The Bonn research team and collaborators from other institutions explored a signaling pathway in fat cells crucial for metabolism. They identified a protein called EPAC1 that promotes the growth of brown fat cells, even converting white fat cells into beige cells. This pathway was observed in mice and human fat cells and in organ-like structures mimicking human brown fat. 

Notably, humans’ non-functional EPAC1 gene variant was linked to a higher body mass index (BMI). Professor Pfeifer sees EPAC1 as a promising target to increase brown fat and energy expenditure, aiming to develop therapies for metabolic diseases amid the global rise in Obesity. The study was part of the DFG Collaborative Research Center Transregio-SFB 333 ‘Brown and Beige Fat – Organ Interactions, Signaling Pathways, and Energy Balance (BATenergy).

In conclusion, the study identified a key regulator for the body’s natural ‘oven’ – brown fat. The protein EPAC1 was found to be responsible for the growth of brown fat cells, offering the potential for increasing brown fat mass and energy expenditure. This discovery holds promise for developing therapies to address metabolic diseases and combat the rising global issue of Obesity.

Journal reference:

  1. Reverte-Salisa, L., Siddig, S., Hildebrand, S. et al. EPAC1 enhances brown fat growth and beige adipogenesis. Nature Cell Biology. DOI: 10.1038/s41556-023-01311-9.

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