The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Endocrinology |
Volume | 155 |
Issue number | 12 |
Pages (from-to) | 4856-67 |
Number of pages | 12 |
ISSN | 0013-7227 |
DOIs | |
Publication status | Published - Dec 2014 |
- Animals, Blood Glucose, Body Composition, Body Size, Cytokines, Diet, High-Fat, Gliosis, Growth Hormone, Hypothalamic Diseases, Hypothalamus, Inflammation, Insulin, Insulin-Like Growth Factor I, Lipids, Male, Mice, Inbred C57BL, Mice, Knockout, Neuropeptides, Journal Article, Research Support, Non-U.S. Gov't
Research areas
ID: 179526026