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Baquedano E.,Autonomous University of Madrid | Baquedano E.,Hospital Infantil Universitario Nino Jesus 28009 | Ruiz-Lopez A.M.,Autonomous University of Madrid | Ruiz-Lopez A.M.,Hospital Infantil Universitario Nino Jesus 28009 | And 10 more authors.
Endocrinology | Year: 2014

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, highGHlevels, 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 inflammationandgliosis. BecauseGHandIGF-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, bothWTandGHR-/- mice had increased weight gain, with GHR-/- mice having a greater rise in their percentage of body fat. InWT mice,HFD-inducedweightgainwasassociatedwithincreasedhypothalamiclevelsofphospho-JNKand 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 HFDinduced obesity. Copyright © 2014 by the Endocrine Society

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