The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice
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The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice. / Baquedano, Eva; Ruiz-Lopez, Ana M; Sustarsic, Elahu G; Herpy, James; List, Edward O.; Chowen, Julie A; Frago, Laura M; Kopchick, John J.; Argente, Jesús.
In: Endocrinology, Vol. 155, No. 12, 12.2014, p. 4856-67.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice
AU - Baquedano, Eva
AU - Ruiz-Lopez, Ana M
AU - Sustarsic, Elahu G
AU - Herpy, James
AU - List, Edward O.
AU - Chowen, Julie A
AU - Frago, Laura M
AU - Kopchick, John J.
AU - Argente, Jesús
PY - 2014/12
Y1 - 2014/12
N2 - 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.
AB - 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.
KW - Animals
KW - Blood Glucose
KW - Body Composition
KW - Body Size
KW - Cytokines
KW - Diet, High-Fat
KW - Gliosis
KW - Growth Hormone
KW - Hypothalamic Diseases
KW - Hypothalamus
KW - Inflammation
KW - Insulin
KW - Insulin-Like Growth Factor I
KW - Lipids
KW - Male
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Neuropeptides
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1210/en.2014-1367
DO - 10.1210/en.2014-1367
M3 - Journal article
C2 - 25237935
VL - 155
SP - 4856
EP - 4867
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0013-7227
IS - 12
ER -
ID: 179526026