title: Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity.
abstract: OBJECTIVE
  Mice deficient of the serotonin transporter (5-HTT ko) mice have a reduced brain serotonin content and develop late-onset obesity. To elucidate the pathophysiology of this obesity, we analyzed the expression of the interrelated weight-regulatory molecules: brain-derived neurotrophic factor (BDNF) and leptin receptor (LR) in brain areas associated with nutrition and activity.
  
  
  METHODS
  We investigated feeding behavior, physical activity and metabolic parameters of 5-HTT ko and wild-type mice and measured the expression of BDNF and LR in brain areas associated with nutrition and activity using quantitative real-time PCR. The influence of age, gender and fasting was analyzed.
  
  
  RESULTS
  Male 5-HTT ko mice developed obesity without hyperphagia from the age of 5 months. Physical activity was reduced in old male, but not old female, 5-HTT ko mice. The BDNF gene expression in frontal cortex was elevated in young, but reduced in old 5-HTT ko mice. Fasting failed to increase the BDNF gene expression in frontal cortex of young 5 HTT ko mice and in the hypothalamus in old 5-HTT ko mice. The fasting-induced hypothalamic increase of LR was absent in both young and old 5-HTT ko mice.
  
  
  CONCLUSIONS
  We propose that low brain serotonin level due to the 5-HTT ko genotype leads to reduced physical activity and low BDNF, which together with the lack of fasting-induced hypothalamic BDNF and LR production results in late-onset obesity. Although lack of the 5-HTT is a genetic vulnerability factor for obesity, female gender is protective.
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Uçeyler
authors.forename: M
authors.initials: M
authors.lastname: Schütt
authors.forename: F
authors.initials: F
authors.lastname: Palm
authors.forename: C
authors.initials: C
authors.lastname: Vogel
authors.forename: M
authors.initials: M
authors.lastname: Meier
authors.forename: A
authors.initials: A
authors.lastname: Schmitt
authors.forename: K-P
authors.initials: KP
authors.lastname: Lesch
authors.forename: R
authors.initials: R
authors.lastname: Mössner
authors.forename: C
authors.initials: C
authors.lastname: Sommer
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000378:metabolism*; D005247:Feeding Behavior; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D054411:Receptors, Leptin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D026901:Membrane Transport Proteins; D054411:Receptors, Leptin; D050486:Serotonin Plasma Membrane Transport Proteins; C515447:leptin receptor, mouse