ESPE Abstracts (2014) 82 P-D-2-1-416

Absence of GH Signaling Induces Hypothalamic Inflammation that is Reversed in Response to a High Fat Diet

Eva Baquedanoa, Ana Ruiz-Lópeza, Elena Pardo-Barquína, Elahu S Gosneyb, James Herpyb, Julie A Chowena, Jesús Argentea, John J Kopchickb & Laura M Fragoa


aDepartment of Endocrinology and Pediatrics, Instituto de Investigación Sanitaria Princesa (IP), Centro de Investi, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, Madrid, Spain; bThe Edison Biotechnology Institute, Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Biomedical Sciences, Athens, Ohio, USA


Background: The GH/IGF1 axis has important roles in growth, metabolism, lipid profile and body composition. GH receptor disrupted mice (GHRKO mice) are resistant to the action of GH, thereby, GHRKO mice are dwarf, hypoinsulinemic, hypoglycemic and obese. Consumption of a high fat diet (HFD) induces inflammatory processes in a multitude of peripheral tissues, including hypothalamus.

Objective and hypotheses: Our aim was to evaluate the effect of HFD intake on hypothalamic inflammation in the absence of GH signalling.

Method: Male C57BL/6J WT and GHRKO mice, 30 days of age were feed with standard chow (normal diet; ND) or HFD (60% fat) during 50 days and were then sacrificed. Levels of cytokines were measured in the hypothalamus by multiplex assay.

Results: The absence of GH signalling in young mice has an impact on lipid metabolism that leads to an increase in circulating NEFA levels (WTND: 1.1±0.08; WTHF: 0.9±0.05; KOND: 1.8±0.16; KOHF: 1.3±0.01. P<0.01) that could induce hypothalamic inflammation. While HFD had no effect in WT mice, it decreased serum NEFA levels and hypothalamic cytokines in GHRKO mice (Table 1).

Table 1. Levels of cytokines (pg/mg protein) in the hypothalamus.
WTNDWTHFKONDKOHF
TNFα7.76±0.217.84±0.399.75±0.45*7.16±0.41
IL1β31.97±1.8232.52±1.5136.91±1.29*26.43±1.47*†,‡
IL63.47±0.233.24±0.194.01±0.222.62±0.06*†,‡
MCP16.86±0.256.75±0.338.07±0.36*6.05±0.34
IL107.22±0.297.61±0.329.07±0.70*6.70±0.21†,‡
IFNγ0.21±0.010.24±0.020.27±0.01*0.19±0.01†,‡
ANOVA: *P<0.01; vs WT ND; P<0.01 vs KO ND; P<0.01 vs WT HFD. n=5–6/group.

Conclusion: As increased NEFA levels have been associated with hypothalamic inflammation, the decreased hypothalamic cytokine levels could be due to the decline in NEFA induced by HFD in GHRKO mice.

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