title: AgRP and NPY expression in the human hypothalamic infundibular nucleus correlate with body mass index, whereas changes in αMSH are related to type 2 diabetes.
abstract: BACKGROUND
  Rodent data show that altered hypothalamic signaling contributes to the development of obesity and insulin resistance.
  
  
  OBJECTIVE
  To determine differences in hypothalamic expression levels of neuropeptide Y (NPY), agouti-related peptide (AgRP), and αMSH in the infundibular nucleus, the human equivalent of the arcuate nucleus, in relation to body mass index (BMI). In addition, the expression in the infundibular nucleus of eight subjects diagnosed with type 2 diabetes was measured to determine possible interference of type 2 diabetes with the association observed between neuropeptides and BMI.
  
  
  METHODS
  We studied AgRP, NPY, and αMSH expression by means of quantitative immunocytochemistry in postmortem hypothalami of 30 subjects with known BMI. In separate experiments, we compared neuropeptide expression in eight subjects with type 2 diabetes with eight matched controls.
  
  
  RESULTS
  We found that AgRP immunoreactivity showed a U-shaped correlation with BMI. No evidence was found for possible influences of corticosteroid treatment. NPY immunoreactivity was significantly lower in overweight and obese subjects. αMSH did not correlate with BMI but was significantly lower in subjects with type 2 diabetes compared with controls. By contrast, NPY and AgRP expression was not affected in type 2 diabetes.
  
  
  CONCLUSIONS
  Our results indicate that the expression of AgRP and NPY are correlated with body weight changes, rather than the presence of type 2 diabetes, whereas changes in αMSH immunoreactivity are related to the presence of type 2 diabetes, indicating separate hypothalamic mechanisms.
authors.affiliation: Alan Turing Institute Almere, Louis Armstrongweg 84, 1311 RL Almere, The Netherlands. jmalkemade@gmail.com
authors.forename: Anneke
authors.initials: A
authors.lastname: Alkemade
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yi
authors.forename: Lei
authors.initials: L
authors.lastname: Pei
authors.forename: Magdalena
authors.initials: M
authors.lastname: Harakalova
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.forename: Susanne E
authors.initials: SE
authors.lastname: la Fleur
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.forename: Andries
authors.initials: A
authors.lastname: Kalsbeek
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054369:Agouti-Related Protein / Q000378:metabolism*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000378:metabolism*; D010904:Pituitary Gland, Posterior / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000521:alpha-MSH / Q000378:metabolism*
chemical_list: C515198:AGRP protein, human; D000305:Adrenal Cortex Hormones; D054369:Agouti-Related Protein; D007004:Hypoglycemic Agents; D009478:Neuropeptide Y; D000521:alpha-MSH