Therapeutic effects of granulocyte-colony stimulating factor on non-alcoholic hepatic steatosis in the rat

Song, Yi; Fang, Cheng Hu; So, Byung Im; Park, Jun Yong; Jun, Dae Won; Kim, Kyung Soo

doi:10.1016/s1665-2681(19)31393-6

Cited by 20 publications

(18 citation statements)

References 42 publications

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“…G-CSF serum levels significantly decreased only several hours after intra-peritoneal G-CSF injection [43] , it is difficult to suggest that the effects of G-CSF treatment are associated with metabolic effects of circulating G-CSF. However, we reported that diabetes-related conditions, diabetic nephropathy, steatohepatitis and diabetic cardiomyopathy were improved in OLETF rats 4 weeks after G-CSF treatment in the same manner [44] – [46] , and the long-lasting effects of G-CSF in this study were also similar to those in our previous reports. Further investigations are necessary to determine the long-lasting effects of G-CSF.…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2014

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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.

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Section: Discussionsupporting

confidence: 90%

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

et al. 2014

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“…To examine the pathology of wound healing, 4% paraformaldehyde-fixed paraffin-embedded wound sections of 5 μm thickness were stained with hematoxylin and eosin (H-E) and Masson's trichrome (MT) staining [15]. Five regions from each digitized images were selected at random from the individual sections and were quantified using the Leica image analysis system (Leica DM 4000B, Wetzlar, Germany) [16].…”

Section: Histologymentioning

confidence: 99%

“…Total RNA was purified using the Qiazol reagent (Qiagen, Valencia, CA, USA) following the manufacturer's instructions [15]. RNA concentrations were measured with a Nanodrop ND-2000 spectrophotometer (Thermo Fisher Scientific Inc., Welmington, DE, USA), and purity was determined by measuring ratios of A260 and A280, which ranged from 1.8 to 2.0.…”

Section: Quantitative Real-time Polymerase Chain Reaction For Egf Andmentioning

confidence: 99%

Local injection of granulocyte-colony stimulating factor accelerates wound healing in a rat excisional wound model

Shen

Park

Song

et al. 2016

Tissue Eng Regen Med

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The skin functions as a protective barrier against the environment. Loss of the integrity of large areas of skin may lead to increased risk of illness [1]. Wound healing is essential to prevent invasion of pathogens and to maintain the integrity of normal tissue [2], and involves several steps including inflammation, formation of granulation tissue, remodeling of connective tissue, collagenization, and formation of new blood vessels [3]. Granulocyte-colony stimulating factor (G-CSF) directly stimulates neutrophil-restricted progenitor cells into proliferation and differentiation [4]. It has been reported to be effective in the treatment of tissue repair in post-myocardial infarction by enhancing mobilization of neutrophils and macrophages from bone marrow [5]. Recently, Wang et al. [6] demonstrated that systemic injection of G-CSF can accelerate wound healing in mice. They suggested that G-CSF repairs wounds through mobilization of bone marrow derived cells (BMDCs) and up-regulation of growth factors. Recent findings, however, have indicated that G-CSF acts directly on cardiomyocytes and monocytes by binding to a receptor expressed on these cells [7-9]. Moreover, Mueller et al. [10] reported that keratinocyte express G-CSF receptors (G-CSFR). The therapeutic effects of local injection of G-CSF on wound healing in a rat wound model remain unclear. In this study, we investigated whether local injection of G-CSF can accelerate wound healing in a rat wound model, and evaluated whether the effects of local injection of G-CSF on wound healing occurred faster than that those of systemic injection. We also investigated the presence of G-CSFRs in wound tissues. MATERIALS AND METHODS Animals Male Sprague-Dawley rats (Koatech, Pyeongtaek, Korea), 10 weeks of age and weighing 280-300 g, were used. The rats were

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“…The OLETF rat is a good model of non-alcoholic fatty liver disease and exhibits insulin resistance, abundant visceral fat tissue, post-prandial hyperglycemia, and hepatic steatosis. ( 25 ) Many investigators have used this model to demonstrate the beneficial effects of treatment with anti-diabetic drug metformin, ( 26 ) granulocyte colony-stimulating factor, ( 27 ) nitric oxide synthase inhibition, ( 28 ) exercise training, ( 3 , 29 ) and caloric restriction on hepatic stenosis. ( 30 ) It has also been reported that hepatic steatosis in OLETF rats was prevented by several food factors, including α-lipoic acid and milk thistle extracts silymarin.…”

Section: Discussionmentioning

confidence: 99%

Identification of cysteinylated transthyretin, a predictive biomarker of treatment response to partially hydrolyzed guar gum in type 2 diabetes rats, by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

Naito

Akagiri

Uchiyama

et al. 2016

J. Clin. Biochem. Nutr.

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Recent evidence has indicated that total fiber intake is inversely related to type 2 diabetes risk. The present study aimed to investigate the effects of chronic administration of partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, on the occurrence of diabetes and its complications, fatty liver and nephropathy. We also identified predictive serum biomarkers of treatment response to PHGG by mass spectroscopy-based proteomic analysis using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a good model of human non-insulin-dependent diabetes mellitus. In this study, at 5 weeks of age, OLETF rats and control strain Long-Evans Tokushima Otsuka (LETO) rats were fed a control diet or a high-fiber diet (5% PHGG) for 57 weeks. Body weight, food intake, oral glucose tolerance test, plasma insulin levels, and urine glucose and protein levels were regularly measured. Oral glucose tolerance tests (OGTT) and storage of serum in a deep freezer were conducted at the beginning of the experiment and every 4 weeks after overnight fasting during the experiments. PHGG treatment affected neither meal patterns nor the body weight of OLETF and LETO rats. Repeated measure analysis of variance revealed significant differences in fasting plasma glucose and plasma glucose at 2 h after OGTT between control OLETF (OLETF-C) rats and OLETF rats treated with PHGG (OLETF-F). The glucose response determined by the area under the curve of OGTT was significantly greater in OLETF-C rats than that in OLETF-F rats at 25 weeks of age. HOMA-IR, an index of insulin resistance, increased at 25 weeks of age in OLETF-C rats, while this increase was significantly inhibited in OLETF-F rats. At 62 weeks of age, PHGG treatment significantly improved hepatic steatosis as well as renal mesangial matrix accumulation in OLETF rats. To identify the risk marker for diabetes mellitus by SELDI-TOF MS, we collected sera from 21-week-old individuals. Among the 12 specific peaks that were risk marker candidates for diabetes mellitus, the m/z 13,720 peak was identified as that of cysteinylated transthyretin by sequencing of four tryptic peptides using tandem mass spectrometry and peak distribution around the m/z 13,720 peak in the SELDI-TOF spectra. In conclusion, we found that chronic treatment with PHGG improved insulin resistance, delayed the onset of diabetes, and inhibited the development of diabetic complications, as well as identified cysteinylated transthyretin as a predictive biomarker of treatment response to PHGG in OLETF rats.

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Therapeutic effects of granulocyte-colony stimulating factor on non-alcoholic hepatic steatosis in the rat

Cited by 20 publications

References 42 publications

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

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

Local injection of granulocyte-colony stimulating factor accelerates wound healing in a rat excisional wound model

Identification of cysteinylated transthyretin, a predictive biomarker of treatment response to partially hydrolyzed guar gum in type 2 diabetes rats, by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

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