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Anti-Obesity Effects of Granulocyte-Colony Stimulating Factor in Otsuka-Long-Evans-Tokushima Fatty Rats

Title
Anti-Obesity Effects of Granulocyte-Colony Stimulating Factor in Otsuka-Long-Evans-Tokushima Fatty Rats
Author
송이선
Keywords
CILIARY NEUROTROPHIC FACTOR; UNCOUPLING PROTEIN-1 UCP1; TYPE-2 DIABETES-MELLITUS; TUMOR-NECROSIS-FACTOR; BROWN ADIPOSE-TISSUE; FACTOR G-CSF; BODY-WEIGHT; FOOD-INTAKE; ENERGY-EXPENDITURE; INSULIN-RESISTANCE
Issue Date
2014-08
Publisher
PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
Citation
PLOS ONE, 2014, 9(8), p1-11
Abstract
Granulocyte-colony stimulating factor (G-CSF) has molecular structures and intracellular signaling pathways that are similar to those of leptin and ciliary neurotropic factor (CNTF). It also has immune-modulatory properties. Given that leptin and CNTF play important roles in energy homeostasis and that obesity is an inflammatory condition in adipose tissue, we hypothesized that G-CSF could also play a role in energy homeostasis. We treated 12 38-week-old male Otsuka-Long-Evans-Tokushima fatty rats (OLETF, diabetic) and 12 age-matched male Long-Evans-Tokushima rats (LETO, healthy) with 200 mu g/day G-CSF or saline for 5 consecutive days. Body weight reduction was greater in G-CSF-treated OLETF (G-CSF/OLETF) than saline-treated OLETF (saline/OLETF) following 8 weeks of treatment (-6.9 +/- 1.6% vs. -3.1 +/- 2.2%, p<0.05). G-CSF treatment had no effect on body weight in LETO or on food intake in either OLETF or LETO. Body fat in G-CSF/OLETF was more reduced than in saline/OLETF (-32.2 +/- 3.1% vs. -20.8 +/- 6.2%, p<0.05). Energy expenditure was higher in G-CSF/OLETF from 4 weeks after the treatments than in saline/OLETF. Serum levels of cholesterol, triglyceride, interleukin-6 and tumor necrosis factor-a were lower in G-CSF/OLETF than in saline/OLETF. Uncoupling protein-1 (UCP-1) expression in brown adipose tissue (BAT) was higher in G-CSF/OLETF than in saline/OLETF, but was unaffected in LETO. Immunofluorescence staining and PCR results revealed that G-CSF receptors were expressed in BAT. In vitro experiments using brown adipocyte primary culture revealed that G-CSF enhanced UCP-1 expression from mature brown adipocytes via p38 mitogen-activated protein kinase pathway. In conclusion, G-CSF treatment reduced body weight and increased energy expenditure in a diabetic model, and enhanced UCP-1 expression and decreased inflammatory cytokine levels may be associated with the effects of G-CSF treatment.
URI
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0105603#ackhttp://hdl.handle.net/20.500.11754/46903
ISSN
1932-6203
DOI
10.1371/journal.pone.0105603
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RESEARCH INSTITUTE[S](부설연구소) > ETC
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