title: Anti-obesity effects of granulocyte-colony stimulating factor in Otsuka-Long-Evans-Tokushima fatty rats.
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 µg/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-α 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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea; Department of Cardiology, Sung-Ae Hospital, Seoul, South Korea.
authors.forename: Yonggu
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.
authors.forename: Yi-Sun
authors.initials: YS
authors.lastname: Song
authors.affiliation: Division of Cardiology, Yanbian University, Yanji, China.
authors.forename: Cheng-Hu
authors.initials: CH
authors.lastname: Fang
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.
authors.forename: Byung-Im
authors.initials: BI
authors.lastname: So
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Joo
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.
authors.forename: In-Hwa
authors.initials: IH
authors.lastname: Park
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Shen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Thoracic Surgery, Hanyang University Hospital, Seoul, South Korea.
authors.forename: Hyuck
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Endocrinology, Hanyang University Hospital, Seoul, South Korea.
authors.forename: You-Heon
authors.initials: YH
authors.lastname: Ahn
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Kim
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D007473:Ion Channels / Q000096:biosynthesis; D008297:Male; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D020334:Rats, Inbred OLETF; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000071256:Uncoupling Protein 1
chemical_list: D015850:Interleukin-6; D007473:Ion Channels; D024101:Mitochondrial Proteins; D014409:Tumor Necrosis Factor-alpha; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D016179:Granulocyte Colony-Stimulating Factor; D002784:Cholesterol