This new key function has been discovered in mice by researchers at the Laboratoire Biologie Fonctionnelle Adaptative (CNRS/Université Paris Diderot) . Published on the website of EMBO Journal on 18 September 2012, this work lends weight to the hypothesis that the brain could be the seat of the initial malfunction leading to obesity-related diseases such as type 2 diabetes, cardiovascular diseases and dyslipidemias.
Obesity is now considered to be a worldwide ‘epidemic’ and the related mortality mostly results from secondary metabolic complications such as diabetes, dyslipidemias and cardiovascular diseases (metabolic syndrome). However, excessive food intake alone cannot explain the link between obesity and its associated diseases. It is not only a matter of how much we eat but also how the body is able to deal with this intake, in particular the choice between utilization or storage of lipids and sugars.
Now, a team from the Laboratoire Biologie Fonctionnelle Adaptative (CNRS/Université Paris Diderot) (1) has identified the role played by a group of neurons in the brain (located in the hypothalamus and producing the neuropeptide AgRP (2), which control the fate of nutrients in organs such as the pancreas, liver and muscles. The researchers showed that mice lacking AgRP neurons and fed a normal diet become obese. On the other hand, when fed a high fat (hyperlipidemic) diet, the mice improve their glucose metabolism. These experiments therefore show that AgRP neurons, which are already known to control food intake, also act on nutrient partitioning, especially through their role in orchestrating the pancreas, liver and various types of muscle. The loss of AgRP neurons changes the central instructions that define the balance between the utilization of sugars or of lipids, thus making the animal better adapted to a high-fat diet.
An imbalance in the ability of the brain to coordinate these tissues could explain the simultaneous appearance of metabolic disorders in several organs, as happens in the onset of metabolic syndrome, i.e. the whole set of obesity-related disorders. Understanding these processes could therefore provide therapeutic approaches for the treatment of such metabolic diseases.
To find out more about the Laboratoire Biologie Fonctionnelle et Adaptative team:
(1) Researchers from the Laboratoire de Signalisation et de Physiopathologie Cardiaque (Inserm/Université Paris Sud), the Centre de Recherche Biomédicale des Cordeliers (Inserm/UPMC/Université Paris Descartes) and the Université Catholique de Louvain also took part in this work.
(2) AgRP stands for Agouti-related protein.
“Hypothalamic AgRP-neurons control peripheral substrate utilization and nutrient partitioning”
Aurélie Joly-Amado, Raphaël G.P. Denis, Julien Castel, Amélie Lacombe, Céline Cansell, Claude Rouch, Nadim Kassis, Julien Dairou, Patrice D. Cani, Renée Ventura-Clapier, Alexandre Prola, Melissa Flamment, Fabienne Foufelle, Christophe Magnan, Serge Luquet
EMBO Journal, on line 18 September 2012