title: Leptin affects insulin action in astrocytes and impairs insulin-mediated physical activity.
abstract: OBJECTIVE
  Impaired insulin action is an early event in the pathogenesis of obesity and type 2-diabetes, and among the metabolic confounders in obese, hyperleptinaemia is constantly present; however its impact on insulin action in the brain and locomotor activity is unknown.
  
  
  METHODS
  We examined insulin action by Western Blot analysis and glycogen synthesis in primary astrocytes and brain tissue and detected locomotion in C57BL/6 mice. The insulin-mediated desire to move was evaluated in healthy volunteers and correlated to leptin levels.
  
  
  RESULTS
  Leptin treatment led to a significant decrease in insulin-mediated phosphorylation of the insulin receptor and Akt473 which was accompanied by a decline in glycogen synthesis in primary astrocytes and significantly decreased insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-2 in brain tissues of mice. Intracerebroventricular insulin failed to promote locomotion in the presence of elevated leptin levels. Lean human subjects reported an increase in the desire to move following insulin which failed in obese and there was an inverse correlation between the insulin-mediated desire to move and leptin levels.
  
  
  CONCLUSIONS
  Our data suggest a crosstalk of leptin and insulin in the brain which leads to a decline in locomotor activity. This might represent a molecular mechanism in obese to inhibit physical activity.
authors: University of Tuebingen, Department of Internal Medicine 4, Tuebingen, Germany.
authors: Tina
authors: T
authors: Sartorius
authors: Martin
authors: M
authors: Heni
authors: Otto
authors: O
authors: Tschritter
authors: Hubert
authors: H
authors: Preissl
authors: Sabine
authors: S
authors: Hopp
authors: Andreas
authors: A
authors: Fritsche
authors: Paul-Simon
authors: PS
authors: Lievertz
authors: Arieh
authors: A
authors: Gertler
authors: Flavien
authors: F
authors: Berthou
authors: Mohammed
authors: M
authors: Taouis
authors: Harald
authors: H
authors: Staiger
authors: Hans-Ulrich
authors: HU
authors: Häring
authors: Anita M
authors: AM
authors: Hennige
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse; D020738:Leptin; D006003:Glycogen; D002097:C-Reactive Protein; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt