title: Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans.
abstract: OBJECTIVE
  To use quantitative magnetic resonance imaging (MRI) to test whether mediobasal hypothalamic (MBH) gliosis is associated with obesity and insulin resistance in humans.
  
  
  METHODS
  Sixty-seven participants underwent a fasting blood draw and MRI. Cases with radiologic evidence of MBH gliosis (N = 22) were identified as the upper tertile of left MBH T2 relaxation time and were compared to controls (N = 23) from the lowest tertile. In a separate postmortem study, brain slices (N = 10) through the MBH were imaged by MRI and stained for glial fibrillary acidic protein (GFAP).
  
  
  RESULTS
  In all participants, longer T2 relaxation time in the left MBH was associated with higher BMI (P = 0.01). Compared with controls, cases had longer T2 relaxation times in the right MBH (P < 0.05), as well as higher BMI (P < 0.05), fasting insulin concentrations (P < 0.01), and HOMA-IR values (P < 0.01), adjusted for sex and age. Elevations in insulin and HOMA-IR were also independent of BMI. In the postmortem study, GFAP staining intensity was positively associated with MBH T2 relaxation time (P < 0.05), validating an MRI-based method for the detection of MBH gliosis in humans.
  
  
  CONCLUSIONS
  These findings link hypothalamic gliosis to insulin resistance in humans and suggest that the link is independent of the level of adiposity.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.|Division of General Internal Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Schur
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.|Division of General Internal Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Melhorn
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington, USA.
authors.forename: Seok-Kyun
authors.initials: SK
authors.lastname: Oh
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, USA.
authors.forename: J Matthew
authors.initials: JM
authors.lastname: Lacy
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.|Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Berkseth
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.|Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington, USA.
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Guyenet
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Sonnen
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.|Division of General Internal Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Vidhi
authors.initials: V
authors.lastname: Tyagi
authors.forename: Mary
authors.initials: M
authors.lastname: Rosalynn
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.|Division of General Internal Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: B
authors.initials: B
authors.lastname: De Leon
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Webb
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.|Division of General Internal Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Zenobia T
authors.initials: ZT
authors.lastname: Gonsalves
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, USA.
authors.forename: Corinne L
authors.initials: CL
authors.lastname: Fligner
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.|Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schwartz
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Maravilla
mesh_terms: D050154:Adiposity / Q000502:physiology; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005215:Fasting / Q000378:metabolism; D005260:Female; D005911:Gliosis / Q000175:diagnosis*; D006801:Humans; D007031:Hypothalamus / Q000473:pathology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D007328:Insulin