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FGF21 Mediates Key Metabolic Actions of Glucagon

Interaction between the hormones glucagon and fibroblast growth factor 21 (FGF21) critically regulates lipid metabolism and body weight. The result of their combined effect is decreased food intake and increased fat burning, which is why these hormones are considered promising candidates for the treatment of obesity and type 2 diabetes. This finding was made by scientists of the Institute of Diabetes and Obesity (IDO) at Helmholtz Zentrum München, a partner in the DZD, in cooperation with the Metabolic Diseases Institute of the University of Cincinnati, Ohio, USA. The results were published in the current issue of the journal ‘Diabetes’.

 

Glucagon as fasting hormone mediates a degradation of the body’s energy reserves. The researchers showed for the first time that direct interaction with the fibroblast growth factor FGF21 is required to achieve this effect. The team led by Professor Tschöp, director of the IDO, investigated the long-term effects of glucagon in a mouse model. Their data revealed reduced food intake, increased fat burning and lowered cholesterol levels. At the same time, significantly increased quantities of the hormone FGF21 were released, and this effect could also be confirmed in humans. If the animals lacked FGF21 due to a genetic defect, glucagon lost its positive metabolic properties. “Our results show that FGF21 is essential for the effects on fat burning and the cholesterol level mediated by glucagon,” said Dr. Kirk Habegger of the Metabolic Disease Institute and lead author of the study.

Dr. Kerstin Stemmer, co-author of the publication and head of the research group for cancer and metabolic research at Helmholtz Zentrum München, pointed out that the new insights on the FGF21 signaling pathway may provide additional drug targets for the treatment of glucagon-producing tumors.

Previous findings of the research groups already showed that fusion hormones of glucagon and glucagon-like peptides (e.g. GLP-1) have significant potential for the treatment of obesity and diabetes. “Until now it was unknown through which signaling pathway glucagon can so impressively make fat ‘melt away’,” said Professor Tschöp. “Now we know that our old acquaintance FGF21 is crucially involved.” Further studies shall elucidate the details of hormonal interaction to develop a specific drug candidate for the treatment of metabolic diseases.
The numerous complications of obesity, such as type 2 diabetes, are among the most common diseases in Germany. These diseases are the focus of research at Helmholtz Zentrum München. The objective is to develop new approaches for diagnosis, treatment and prevention.

 

Original publication:
Habegger, KM et al (2013). Fibroblast Growth Factor 21 Mediates Specific Glucagon Actions, Diabetes, doi: 10.2337/db12-1116

Link to the original publication