title: Longer T(2) relaxation time is a marker of hypothalamic gliosis in mice with diet-induced obesity.
abstract: A hallmark of brain injury from infection, vascular, neurodegenerative, and other disorders is the development of gliosis, which can be detected by magnetic resonance imaging (MRI). In rodent models of diet-induced obesity (DIO), high-fat diet (HFD) consumption rapidly induces inflammation and gliosis in energy-regulating regions of the mediobasal hypothalamus (MBH), and recently we reported MRI findings suggestive of MBH gliosis in obese humans. Thus, noninvasive imaging may obviate the need to assess MBH gliosis using histopathological end points, an obvious limitation to human studies. To investigate whether quantitative MRI is a valid tool with which to measure MBH gliosis, we performed analyses, including measurement of T(2) relaxation time from high-field MR brain imaging of mice fed HFD and chow-fed controls. Mean bilateral T(2) relaxation time was prolonged significantly in the MBH, but not in the thalamus or cortex, of HFD-fed mice compared with chow-fed controls. Histological analysis confirmed evidence of increased astrocytosis and microglial accumulation in the MBH of HFD-fed mice compared with controls, and T(2) relaxation times in the right MBH correlated positively with mean intensity of glial fibrillary acidic protein staining (a marker of astrocytes) in HFD-fed animals. Our findings indicate that T(2) relaxation time obtained from high-field MRI is a useful noninvasive measurement of HFD-induced gliosis in the mouse hypothalamus with potential for translation to human studies.
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA 98104, USA.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Lee
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Thaler
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Berkseth
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Melhorn
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schwartz
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Schur
mesh_terms: D000818:Animals; D001823:Body Composition / Q000502:physiology; D059305:Diet, High-Fat; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000473:pathology*; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000473:pathology*
chemical_list: D005904:Glial Fibrillary Acidic Protein
keywords: gliosis; high-fat diet; hypothalamus; magnetic resonance imaging; obesity
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