title: The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice.
abstract: GH is important in metabolic control, and mice with disruption of the gene encoding the GH receptor (GHR) and GH binding protein (GHR-/- mice) are dwarf with low serum IGF-1 and insulin levels, high GH levels, and increased longevity, despite their obesity and altered lipid and metabolic profiles. Secondary complications of high-fat diet (HFD)-induced obesity are reported to be associated with hypothalamic inflammation and gliosis. Because GH and IGF-1 can modulate inflammatory processes, our objective was to evaluate the effect of HFD on hypothalamic inflammation/gliosis in the absence of GH signaling and determine how this correlates with changes in systemic metabolism. On normal chow, GHR-/- mice had a higher percentage of fat mass and increased circulating nonesterified free fatty acids levels compared with wild type (WT), and this was associated with increased hypothalamic TNF-α and phospho-JNK levels. After 7 weeks on a HFD, both WT and GHR-/- mice had increased weight gain, with GHR-/- mice having a greater rise in their percentage of body fat. In WT mice, HFD-induced weight gain was associated with increased hypothalamic levels of phospho-JNK and the microglial marker Iba-1 (ionized calcium-binding adapter molecule 1) but decreased cytokine production. Moreover, in GHR-/- mice, the HFD decreased hypothalamic inflammatory markers to WT levels with no indication of gliosis. Thus, the GH/IGF-1 axis is important in determining not only adipose tissue accrual but also the inflammatory response to HFD. However, how hypothalamic inflammation/gliosis is defined will determine whether it can be considered a common feature of HFD-induced obesity.
authors.affiliation: Department of Pediatrics (E.B., A.M.R.-L., J.A.C., L.M.F., J.A.), Universidad Autónoma de Madrid; Department of Endocrinology, Hospital Infantil Universitario Niño Jesús 28009, Madrid, Spain; Instituto de Investigación Sanitaria Princesa; and Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28009 Madrid, Spain; and The Edison Biotechnology Institute (E.G.S., J.H., E.O.L., J.J.K.) and Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701.
authors.forename: Eva
authors.initials: E
authors.lastname: Baquedano
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ruiz-Lopez
authors.forename: Elahu G
authors.initials: EG
authors.lastname: Sustarsic
authors.forename: James
authors.initials: J
authors.lastname: Herpy
authors.forename: Edward O
authors.initials: EO
authors.lastname: List
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
authors.forename: Laura M
authors.initials: LM
authors.lastname: Frago
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001823:Body Composition; D049628:Body Size; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D005911:Gliosis / Q000209:etiology*; D013006:Growth Hormone / Q000172:deficiency*; D007027:Hypothalamic Diseases / Q000097:blood / Q000209:etiology*; D007031:Hypothalamus / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000097:blood
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D008055:Lipids; D009479:Neuropeptides; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone