title: High-fat-diet exposure induces IgG accumulation in hypothalamic microglia.
abstract: The mediobasal hypothalamic arcuate nucleus (ARC), with its relatively 'leaky' blood-brain barrier that allows more circulating molecules to enter the brain, has emerged as a key sensor of blood-borne signals. In both the ARC and white adipose tissue (WAT), consumption of a high-fat diet (HFD) rapidly induces infiltration of microglia (ARC) or macrophages (WAT). Animals with HFD-induced obesity (DIO) and insulin resistance additionally accumulate B cells in WAT, increasing the local production of pathogenic antibodies. We therefore investigated whether DIO mice or genetically obese ob/ob mice have increased IgG in the ARC, analogous to the recent observations in WAT. Following 16 weeks of exposure to a HFD, wild-type (WT) mice had significantly increased IgG-immunoreactivity (ir) signaling that was specific to the ARC and was exclusively concentrated in microglia. By contrast, IgG-ir of age-matched obese ob/ob mice fed standard chow had ARC IgG levels comparable with those in chow-fed WT control mice. However, following 2 weeks of HFD exposure, ob/ob mice also had a significant increase of IgG-ir in the ARC. In summary, our findings reveal a novel pathophysiological phenomenon, specific for the hypothalamic ARC, that is induced by exposure to a HFD and can be enhanced, but not caused, by genetic obesity.
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Centre for Health and Environment, Technical University Munich, Munich, Germany.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yi
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism / Q000473:pathology; D003720:Densitometry; D059305:Diet, High-Fat; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D015430:Weight Gain
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G