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Leptin resistance causes overweight

Many overweight people lack the feeling of being full. It was long thought that this was due to the disrupted transport of the satiety hormone leptin to the brain. That is not the case, as a group of DZD scientists was able to show using a new 3D imaging method. The cause seems to lie in the nerve cells, as the researchers describe in an article in the "International Journal of obesity".

Lichtscheibenfluoreszenzmikroskopische Aufnahme des Transportes von mit grüner Fluoreszenz markiertem Leptin aus den rot gefärbten Blutgefäßen in das Hirngewebe einer Maus. In den Blutgefäßen verbleibendes Leptin ist gelb gefärbt. Leptin wird hauptsächlich über den, markant in grün erscheinenden, Plexus choroides transportiert und somit über die Hirnflüssigkeit im Gehirn verteilt. Quelle: Helmholtz Zentrum München

"In obese mice and humans, leptin is released from fatty tissue into the bloodstream in high concentrations but fails to activate the satiety centers in the brain. It has long been assumed that leptin resistance is caused by a disrupted transport process," explains Luke Harrison, a doctoral student at Helmholtz Zentrum München and lead author of the study. As the ability of leptin to cross the blood-brain barrier is limited, so the theory goes, less of it reaches the satiety centers. The innovative 3D technique enabled the researchers to visualize the transport of leptin for the first time and to investigate whether this theory holds up.

Working with biologists, pathologists and structural biologists, Harrison was able to disprove this assumption. Thanks to the new imaging method, the research team headed by Dr. Paul Pfluger, a partner in the German Center for Diabetes Research (DZD), showed that leptin reaches the brain in sufficient quantities both in thin and in obese mice. The cause of the eating disorder must therefore lie in the nerve cells themselves. "We can now narrow down the cause of leptin resistance and focus our research on the molecular mechanisms within nerve cells," says Dr. Paul Pfluger. "

Original publication:
Luke Harrison et. al.: Fluorescent blood brain barrier tracing shows intact leptin transport in obese mice. International Journal of obesity. DOI:10.1038/s41366-018-0221-z