title: Selective insulin resistance in homeostatic and cognitive control brain areas in overweight and obese adults.
abstract: OBJECTIVE
  Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance.
  
  
  METHODS
  In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking.
  
  
  RESULTS
  In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only.
  
  
  CONCLUSIONS
  Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior.
authors: Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany German Center for Diabetes Research, Tübingen, Germany Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany stephanie.kullmann@med.uni-tuebingen.de.
authors: Stephanie
authors: S
authors: Kullmann
authors: Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany German Center for Diabetes Research, Tübingen, Germany Department of Internal Medicine IV, University of Tübingen, Tübingen, Germany.
authors: Martin
authors: M
authors: Heni
authors: Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany German Center for Diabetes Research, Tübingen, Germany Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany.
authors: Ralf
authors: R
authors: Veit
authors: Department of High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tübingen, Germany Department of Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany.
authors: Klaus
authors: K
authors: Scheffler
authors: Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany German Center for Diabetes Research, Tübingen, Germany.
authors: Jürgen
authors: J
authors: Machann
authors: Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany German Center for Diabetes Research, Tübingen, Germany Department of Internal Medicine IV, University of Tübingen, Tübingen, Germany.
authors: Hans-Ulrich
authors: HU
authors: Häring
authors: Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany German Center for Diabetes Research, Tübingen, Germany Department of Internal Medicine IV, University of Tübingen, Tübingen, Germany.
authors: Andreas
authors: A
authors: Fritsche
authors: Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany German Center for Diabetes Research, Tübingen, Germany.
authors: Hubert
authors: H
authors: Preissl
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D015992:Body Mass Index; D001921:Brain / Q000502:physiology; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D066249:Craving / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000523:psychology; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006815:Hunger / Q000502:physiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007031:Hypothalamus / Q000098:blood supply; D007266:Inhibition, Psychological; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D009765:Obesity / Q000503:physiopathology / Q000523:psychology; D050177:Overweight / Q000503:physiopathology* / Q000523:psychology; D017397:Prefrontal Cortex / Q000098:blood supply
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin