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.

Caffeine-Stimulated Intestinal Epithelial Cells Suppress Lipid Accumulation in Adipocytes

“…G-CSF belongs to the class-1 cytokine superfamily, and the cytokines in this superfamily play an important role in energy homeostasis and exert anti-obesity effects (32,33). Intraperitoneal administration of G-CSF decreased body weight and increased energy expenditure in diabetic model rats (12). These results indicate that caffeine-stimulated medium suppresses lipid accumulation through decreased secretion levels of PAI-1 and IL-8 from Caco-2 cells.…”

“…Cytokines are classified as pro-inflammatory cytokines, such as IL-1, IL-8 and TNF-␣, and anti-inflammatory cytokines, such as IL-4 and IL-10. IL-4 and granulocytecolony stimulating factor (G-CSF) which are known to suppress adipocyte differentiation (11,12). Thus, intestinal epithelial cell-derived cytokines might regulate adipogenesis and adipocyte differentiation.…”

Obesity-Induced Peritoneal Dissemination of Ovarian Cancer and Dominant Recruitment of Macrophages in Ascites

“…4). G-CSF treatment reduced body weight and increased energy expenditure in a diabetic rat model (64). On the other hand, M-CSF KO mice showed reduced body weight and monocytes in blood and spleen but no change in neutrophils compared to WT mice (65).…”

Administration of granulocyte-colony stimulating factor accompanied with a balanced diet improves cardiac function alterations induced by high fat diet in mice

“…Anti-obesity effects of G-CSF have been demonstrated, resulting in the reduction of inflammatory cytokines that led to a loss in body weight in a model of obese-diabetic rats [ 40 ]. The anti-inflammatory effect of G-CSF is well characterized and has been observed in different disease models, including chronic Chagas disease cardiomyopathy, which has been shown in previous studies from our group [ 26 ].…”