Brain Insulin Resistance: Impact of Different Mediators

Datum

20.10.2015

Zeit

16:00 - 17:00

Sprecher

Tina Sartorius

Zugehörigkeit

Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen

Serie

PLID Diabetes Forschungsseminar

Sprache

en

Hauptthema

Biologie

Andere Themen

Biologie, Medizin

Host

Ünal Coskun

Beschreibung

Brain  Insulin  Resistance:  Impact  of  Different  Mediators   Obesity,   inflammation,   and   insulin   resistance   are   major   characteristics   of   type   2   diabetes   mellitus   (T2DM)  and  their  incidences  are  steadily  increasing  worldwide.  To  curtail  the  current  obesity  epidemic,  it   is   therefore   essential   to   identify   mediators   and   the   underlying   mechanisms   contributing   to   the   development   of   insulin   resistance   and   subsequent   T2DM.   While   impaired   insulin   action   in   peripheral   tissues   like   skeletal   muscle,   liver   and   fat   is   well   documented,   the   causes   and   consequences   of   insulin   resistance  in  the  brain  are  far  less  understood.  Insulin  response  in  the  brain  depends  on  body  weight,  the   genetic  background,  age,  and  in  particular  on  levels  of  saturated  free  fatty  acids  (SFA)  that  are  associated   with   impaired   insulin   action   in   the   brain.   Previously,   we   demonstrated   that   high-­‐fat   feeding   in   mice   mediates   insulin   resistance   in   the   brain.   However,   rather   the   fat   quality   than   the   total   fat   content   attracts   notice   to   correlate   with   alterations   in   insulin   sensitivity   and   weight   gain:   a   moderate   SFA-­‐ enrichment   was   shown   to   be   accompanied   by   glucose   intolerance,   reduced   brain   activity   and   central   insulin   resistance   in   mice   whereas   an   isocaloric   diet-­‐enrichment   with   monounsaturated   fatty   acids   protected   from   these   deleterious   effects   (Sartorius   et   al.,   2012,   Diabetes).   One   potential   mediator   that   links  fatty  acids  to  insulin  resistance  is  the  Toll-­‐like  receptor  (TLR)  family.  TLRs,  and  especially  those  that   bind  saturated  free  fatty  acids,  like  TLR2  and  TLR4,  are  expressed  in  almost  all  cell  types  within  the  brain   and   our   data   demonstrated   that   TLR2/4   are   a   causal   link   in   the   progression   toward   obesity   and   brain   insulin   resistance   (Sartorius   et   al.,   2012,   FASEB).   A   critical   but   not   challenged   question   is   whether   the   increased   levels   of   free   fatty   acids   are   reflected   in   the   membrane   lipidome   of   organs   in   dependence   of   TLR2  and/or  TLR4.  Thus,  an  ongoing  DZD  project  currently  determines  the  putative  role  of  an  interaction   between   TLR2   and   4   and   membrane   lipids   in   different   organs   and   brain   areas   and   the   consequences   in   metabolic   perturbations   on   the   molecular,   tissue,   and   systemic   level.   Insights   from   this   survey   will   be   important   to   better   understand   the   role   of   a   lipid-­‐TLR   interaction   in   the   pathophysiology   of   obesity,   insulin  resistance  and  T2DM.  

Letztmalig verändert: 20.10.2015, 10:32:21