Abstract No.: | A-E1165 |
Country: | Canada |
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Title: | EFFECT OF DIET INDUCED OBESITY ON FEVER AND CIRCULATING IL-6 FOLLOWING LPS IN MALE RATS. |
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Authors/Affiliations: | 2 Joanna Pohl*; 1 Claudia Frate; 3 Stephen Poole; 2 Giamal N. Luheshi; 1 Barbara Woodside;
1 Concordia University, Montreal, QC, Canada; 2 Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada; 3 National Institute for Biological Standards and Control, Montreal, QC, Canada
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Content: | Background: It has been widely documented that obesity is often accompanied by a state of underlying inflammation characterized by a small upregulation of cytokines such as IL-6 and IL-1 receptor antagonist (IL-1ra). These cytokines are also known to be involved in the febrile response to exogenous pathogens. Objectives: In the present study we investigated how rats rendered obese by exposure to a highly palatable diet respond to administration of lipopolysaccharide (LPS) in terms of the fever response and pattern of circulating IL-6. Methods: Male Wistar rats (250-300g) were given free access to a liquid diet supplement (Replenish) in addition to standard laboratory chow, until their body weight was 15% higher than that of control rats fed only laboratory chow. Core body temperature was determined using remote radio-biotelemetry with intraperitoneally implanted temperature sensitive radio transmitters (TA10TA-F40, Data Sciences). Levels of circulating IL-6 were measured in blood obtained from the tail vein at 0, 1, 2, 4, 8, 12 and 24 hours following intraperitoneal injection of either LPS (100μg/kg) or endotoxin free physiological saline (1 ml/kg). Circulating cytokine levels were quantified using ELISA. Results: At the time of the experiment, the average body weight was 590.5g and 504.3g and white adipose tissue weight including retroperitoneal and epidydimal regions was 29.2g and 14.4g for the obese and non-obese rats respectively. We demonstrate that obese males exhibit a significantly increased and prolonged fever response to an intraperitoneal injection of LPS (100μg/kg) when compared to their non-obese conspecifics (p< 0.05). In addition, although rats in our model do not have higher baseline circulating levels of IL-6 than non-obese rats (p> 0.05), they exhibit significantly higher levels of IL-6 2 and 4 hours following LPS injection (p< 0.05). Discussion: Our findings suggest that although in our model obese rats do not exhibit a low grade inflammatory state, they do show a greater response to immune challenge than lean rats and that the increase in fever seen in obese rats may, at least in part, reflect increased circulating levels of IL-6. |
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