Alterations in organelle interactions within neurons cause obesity
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.
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