Alterations in organelle interactions within neurons cause obesity

Researchers Marc Schneeberger, from UB, and Marc Claret, Miguel Servet researcher from IDIBAPS.
Researchers Marc Schneeberger, from UB, and Marc Claret, Miguel Servet researcher from IDIBAPS.
Research
(27/09/2013)
Leptin hormone plays a major role in regulating brainʼs hunger feeling. When enough food has been eaten, this molecule, secreted by adipose tissue, inhibits appetite. However, many obese people are resistant to the effects of leptin, although they have a high circulating concentration of leptin. To date, molecular mechanisms responsible for leptin resistance remained unknown.
Researchers Marc Schneeberger, from UB, and Marc Claret, Miguel Servet researcher from IDIBAPS.
Researchers Marc Schneeberger, from UB, and Marc Claret, Miguel Servet researcher from IDIBAPS.
Research
27/09/2013
Leptin hormone plays a major role in regulating brainʼs hunger feeling. When enough food has been eaten, this molecule, secreted by adipose tissue, inhibits appetite. However, many obese people are resistant to the effects of leptin, although they have a high circulating concentration of leptin. To date, molecular mechanisms responsible for leptin resistance remained unknown.
 
The research has been led by Marc Claret, Miguel Servet - ISCIII researcher at IDIBAPS. Ramon Gomis, professor from the Department of Medicine and director of IDIBAPS, and Marc Schneeberger, first author and predoctoral researcher at the UB, collaborated in it. The study describes the primary role that Mitofusin 2 in POMC neurons plays in leptin resistance. The research, carried out within the programme RecerCaixa of Obra Social La Caixa and the Catalan Association of Public Universities (ACUP), has been published on the journal Cell and highlighted on its cover.

To better understand the role of Mitofusin 2 in the development of leptin resistance and obesity, transgenic mice lacking Mitofusin 2 in POMC neurons were generated. These animals eat more, gain weight due to an excessive accumulation of fat, and their systems of satiety and energy expenditure are altered. Disorders are produced by endoplasmic reticulum stress of POMC neurons, which prevents the release of an appetite-suppressing neuropeptide. Endoplasmic reticulum is a cell organelle responsible, among other duties, for the formation and maturation of proteins encoded in the genome and their distribution inside or outside the cell. Pharmacological relieve of endoplasmic reticulum stress reverse these metabolic alterations and mice show a normal feeding behaviour.

Thus, the research proves that a high-fat diet can alter appetite regulation mechanism by means of its effects on Mitofusin 2 protein of hypothalamic POMC neurons. It is the first finding that describes a molecular mechanism which relates endoplasmic reticulum stress, leptin resistance, and appetite and body weight deregulation.

Antonio Zorzano, David Sebastián and Ignacio Castrillón, researchers from the Department of Biochemistry and Molecular Biology at the Faculty of the Biology of the UB and members of the Institute for Research in Biomedicine (IRB), also participated in the research.

Further information

 
Reference:
M. Schneeberger; M. O. Dietrich; D. Sebastián; M. Imbernón; C. Castaño; A. García; Y. Esteban; A. González Franquesa; I. Castrillón Rodríguez; A. Bortolozzi; P. M. Garcia Roves; R. Gomis; R. Nogueiras; T. L. Horvath; A. Zorzano i M. Claret. "Mitofusin-2 in POMC neurons connects ER stress with leptin resistance and energy imbalance". Cell, September 2013. DOI: 10.1016/j.cell.2013.09.003