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Metabolism Research

Plan B for heat generation

Brown adipose tissue is considered an interesting target for the treatment of obesity or type 2 diabetes. Scientists from the Helmholtz Zentrum München Institute for Diabetes and Obesity (IDO), partner in the German Center for Diabetes Research, have now shown that the proteins UCP1 and FGF21 are not crucial for energy homeostasis in the cold, as generally accepted. Their work is published in Cell Metabolism.

Brown adipose tissue. Source: Diapedia / CC BY-NC-SA

Brown adipose tissue is found in almost all mammals, including humans. Its cells produce heat by oxidizing sugars and fatty acids. The thermogenic protein UCP1* plays a key role in this process in order to maintain body temperature when it is cold. In the cold, another hormone is produced in the brown fat, the fibroblast growth factor 21 (FGF21)**. “The media describe brown fat as the Holy Grail in obesity and diabetes research, and FGF21 as a reinforcing hormone,” reports Dr. Martin Jastroch. He is head of the “Mitochondrial Biology” Research Unit at the Institute for Diabetes and Obesity (IDO) at the Helmholtz Zentrum München. Jastroch continues, “Our study refutes this view by showing that FGF21 has no effect on brown fat’s heat generation in cold environments.”

Thermogenesis also possible without UCP1 and FGF21

“In this study, we use new mouse models to show that in the cold, the increase of energy metabolism is possible without UCP1 and FGF21, which was previously assumed to have an essential role,” adds IDO researcher Dr. Susanne Keipert. Together with Jastroch and colleagues, she has examined their role in a number of organ systems. When there is no UCP1 in the mouse, more FGF21 was released, but even if FGF21 was deleted additionally, energy consumption still increases and heat is produced. “Neither UCP1 nor FGF21 are necessary in order to survive in cold climates and to increase the metabolism,” concludes  Jastroch. “Speculative views regarding FGF21 in brown fat have therefore been clarified.”

Jastroch is involved in a further publication in Science Advances that shows the loss of brown fat during evolution in a number of animal groups, although geological history predicts that they must have adapted to the cold.

Using extensive systems biology analyses of gene expression, the scientists found a number of genes that could explain alternative mechanisms of thermogenesis. Keipert adds, “Although obesity and diabetes treatment focuses on brown fat, UCP1 and FGF21, our study has opened up new perspectives for alternative approaches.”

Further Information

* Thermogenin (Uncoupling Protein 1, UCP1) is found in the mitochondrial membrane of brown adipose tissue. It is used to generate heat without muscular activity. This type of heat generation is very important for hibernating animals and in newborn mammals.

** FG21 (Fibroblast growth factor 21) is one of the so-called fibroblast growth factors, a group of proteins with various functions. The hormone is attributed with increased insulin sensitivity, increased energy metabolism and reduced obesity. Elevated FGF21 blood levels are associated with thermogenesis.

Original Publications:
Susanne Keipert et al., Long-term cold adaptation 1 does not require FGF21 (n)or UCP1, Cell Metabolism, doi: 10.1016/j.cmet.2017.07.016

Gaudry MJ, et al., Inactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades.
 Science Advances, doi: 10.1126/sciadv.1602878.

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Institute of Diabetes and Obesity (IDO) studies the diseases of the metabolic syndrome by means of systems biological and translational approaches on the basis of cellular systems, genetically modified mouse models and clinical intervention studies. It seeks to discover new signaling pathways in order to develop innovative therapeutic approaches for the personalized prevention and treatment of obesity, diabetes and their concomitant diseases. IDO is part of the Helmholtz Diabetes Center (HDC).  

The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich.