title: Decreased serotonin transporter immunoreactivity in the human hypothalamic infundibular nucleus of overweight subjects.
abstract: BACKGROUND
  That serotonin plays a role in the regulation of feeding behavior and energy metabolism has been known for a long time. Serotonin transporters (SERT) play a crucial role in serotonin signaling by regulating its availability in the synaptic cleft. The neuroanatomy underlying serotonergic signaling in humans is largely unknown, and until now, SERT immunoreactivity in relation to body weight has not been investigated.
  
  
  OBJECTIVE
  To clarify the distribution of SERT immunoreactivity throughout the human hypothalamus and to compare SERT immunoreactivity in the infundibular nucleus (IFN), the human equivalent of the arcuate nucleus, in lean and overweight subjects.
  
  
  METHODS
  First, we investigated the distribution of serotonin transporters (SERT) over the rostro-caudal axis of six post-mortem hypothalami by means of immunohistochemistry. Second, we estimated SERT immunoreactivity in the IFN of lean and overweight subjects. Lastly, double-labeling of SERT with Neuropeptide Y (NPY) and melanocortin cell populations was performed to further identify cells showing basket-like SERT staining.
  
  
  RESULTS
  SERT-immunoreactivity was ubiquitously expressed in fibers throughout the hypothalamus and was the strongest in the IFN. Immunoreactivity in the IFN was lower in overweight subjects (p = 0.036). Basket-like staining in the IFN was highly suggestive of synaptic innervation. A very small minority of cells showed SERT double labeling with NPY, agouti-related protein and α-melanocyte stimulating hormone.
  
  
  CONCLUSIONS
  SERT is ubiquitously expressed in the human hypothalamus. Strong SERT immunoreactivity, was observed in the IFN a region important for appetite regulation, in combination with lower SERT immunoreactivity in the IFN of overweight and obese subjects, may point toward a role for hypothalamic SERT in human obesity.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Anke J
authors.initials: AJ
authors.lastname: Borgers
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Koopman
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Bisschop
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Mireille J
authors.initials: MJ
authors.lastname: Serlie
authors.affiliation: Department of Neuropsychiatric Disorders, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences Amsterdam, Netherlands.
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: la Fleur
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands ; Cognitive Science Center Amsterdam, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: Alkemade
keywords: SERT; arcuate nucleus; hypothalamus; obesity; paraventricular nucleus