• Molecules and Cells
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• v.37 no.5
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• pp.365-371
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• 2014

Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in adipose tissues are involved in obesity-mediated metabolic complications, including insulin resistance. Here, we summarize recent findings on the key roles of innate (neutrophils, macrophages, mast cells, eosinophils) and adaptive (regulatory T cells, type 1 helper T cells, CD8 T cells, B cells) immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. In particular, the roles of natural killer T cells, one type of innate lymphocyte, in adipose tissue inflammation will be discussed. Finally, a new role of adipocytes as antigen presenting cells to modulate T cell activity and subsequent adipose tissue inflammation will be proposed.

• Preventive Nutrition and Food Science
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• v.17 no.2
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• pp.129-135
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• 2012

GPAR{elidium (G.) amansii is a red alga widely distributed in the shallow waters around East Asian countries. We investigated the effect of G. amansii on lipid accumulation and ROS (Reactive Oxygen Species) production in 3T3-L1 cells. G. amansii extracts dose-dependently inhibited lipid formation and ROS generation in cultured cells. Our results showed that anti-adipogenic effect of G. amansii was due to the reduction in mRNA expressions of PPAR${\gamma}$(peroxisome proliferator-activated receptor-${\gamma}$) and aP2 (adipocyte protein 2). G. amansii extracts significantly decreased mRNA levels of a ROS-generator, NOX4 (nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4), and increased the protein levels of antioxidant enzymes including SOD1/2 (superoxide dismutases), Gpx (glutathione peroxidase), and GR (glutathione reductase), which can lead to the reduction of ROS in the cell. In addition, the G. amansii extract enhanced mRNA levels of adiponectin, one of the adipokines secreted from adipocytes, and GLUT4, glucose uptake protein. Taken together, our study shows that G. amansii extract inhibited lipid accumulation and ROS production by controlling adipogenic signals and ROS regulating genes.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.11-21
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• 2021

Adipose tissue secretes many adipokines which contribute to various metabolic processes, such as blood pressure, glucose homeostasis, inflammation and angiogenesis. The biology of adipose tissue in an obese individual is abnormally altered in a manner that increases the body's vulnerability to immune diseases, such as psoriasis. Psoriasis is considered a chronic inflammatory skin disease which is closely associated with being overweight and obese. Additionally, secretion of leptin, a type of adipokine, increases dependently on adipose cell size and adipose accumulation. Likewise, high leptin levels also aggravate obesity via development of leptin resistance, suggesting that leptin and obesity are closely related. Leptin induction in psoriatic patients is mainly driven by the interleukin (IL)-23/helper T (Th) 17 axis pathway. Furthermore, leptin can have an effect on various types of immune cells such as T cells and dendritic cells. Here, we discuss the relationship between obesity and leptin expression as well as the linkage between effect of leptin on immune cells and psoriasis progression.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.186-196
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• 2023

Dyglomera^® is an aqueous ethanol extract derived from the fruit and pods of Dichrostachys glomerata. A previous study has revealed that Dyglomera regulates adipogenesis and lipolysis by modulating AMP-activated protein kinase (AMPK) phosphorylation and increased expression levels of lipolysis-related proteins in white adipose tissue of high fat diet-induced mice and 3T3-L1 adipocyte cells. To further investigate mechanisms of Dyglomera, additional studies were performed using 3T3-L1 cells. Results revealed that Dyglomera downregulated adipogenesis by inhibiting the protein kinase B/mammalian target of rapamycin signaling pathway and reconfirmed that it downregulated gene expression levels of proliferator-activated receptor (PPAR)-γ, CCAAT enhancer binding protein α, sterol-regulation element-binding protein-1c. Dyglomera also reduced adipokines such as tumor necrosis factor alpha, interleukin-1β, and interleukin 6 by regulating leptin expression. Moreover, Dyglomera promoted beige-and-brown adipocyte-related phenotypes and regulated metabolism by increasing mitochondrial number and expression levels of genes such as T-box protein 1, transmembrane protein 26, PR domain 16, and cluster of differentiation 40 as well as thermogenic factors such as uncoupling protein 1, proliferator-activated receptor-gamma co-activator-1α, Sirtuin 1, and PPARα through AMPK activation. Thus, Dyglomera not only can inhibit adipogenesis, but also can promote lipolysis and thermogenesis and regulate metabolism by affecting adipokine secretion from 3T3-L1 adipocytes.

• Molecules and Cells
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• v.37 no.10
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• pp.734-741
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• 2014

Histone modifications on major transcription factor target genes are one of the major regulatory mechanisms controlling adipogenesis. Plant homeodomain finger 2 (PHF2) is a Jumonji domain-containing protein and is known to demethylate the histone H3K9, a repressive gene marker. To better understand the function of PHF2 in adipocyte differentiation, we constructed stable PHF2 knock-down cells by using the mouse pre-adipocyte cell line 3T3-L1. When induced with adipogenic media, PHF2 knock-down cells showed reduced lipid accumulation compared to control cells. Differential expression using a cDNA microarray revealed significant reduction of metabolic pathway genes in the PHF2 knock-down cell line after differentiation. The reduced expression of major transcription factors and adipokines was confirmed with reverse transcription- quantitative polymerase chain reaction and Western blotting. We further performed co-immunoprecipitation analysis of PHF2 with four major adipogenic transcription factors, and we found that CCATT/enhancer binding protein (C/EBP)${\alpha}$ and C/EBP${\delta}$ physically interact with PHF2. In addition, PHF2 binding to target gene promoters was confirmed with a chromatin immunoprecipitation experiment. Finally, histone H3K9 methylation markers on the PHF2-binding sequences were increased in PHF2 knock-down cells after differentiation. Together, these results demonstrate that PHF2 histone demethylase controls adipogenic gene expression during differentiation.

• CELLMED
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• v.4 no.1
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• pp.3.1-3.8
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• 2014

Spa represents a treatment widely used in many rheumatic diseases (RD). The mechanisms by which immersion in mineral or thermal water ameliorates RD are not fully understood. The net benefit is probably the result of a combination of factors, among which the mechanical, thermal and chemical effects are most prominent. Buoyancy, immersion, resistance and temperature play important roles. According to the gate theory, pain relief may be due to the pressure and temperature of the water on skin; heat may reduce muscle spasm and increase the pain threshold. Mud-bath therapy increases plasma ${\beta}$-endorphin levels and secretion of corticotrophin, cortisol, growth hormone and prolactin. It has recently been demonstrated that thermal mud-bath therapy induces a reduction in circulating levels of prostaglandin E2, leukotriene B4, interleukin-$1{\beta}$ and tumour necrosis factor-${\alpha}$, important mediators of inflammation and pain. Furthermore, balneotherapy has been found to cause an increase in insulin-like growth factor-1, which stimulates cartilage metabolism, and transforming growth factor-${\beta}$. Beneficial anti-inflammatory and anti-degenerative effects of mineral water were confirmed in chondrocytes cultures, too. Various studies in vitro and in humans have highlighted the positive action of mud-packs and thermal baths, especially sulphurous ones, on the oxidant/antioxidant system. Overall, thermal stress has an immunosuppressive effect. Many other non-specific factors may also contribute to the beneficial effects observed after spa therapy in some RD, including effects on cardiovascular risk factors (e.g. adipokines) and changes in the environment, pleasant surroundings and the absence of work duties.

• Nutrition Research and Practice
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• v.3 no.2
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• pp.84-88
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• 2009

In our previous study, we have shown that berberine has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect is due to the down-regulation of adipogenic enzymes and transcription factors. Here we focused more on anti-inflammatory effect of berberine using real time RT-PCR and found it changes expressions of adipokines. We hypothesized that anti-adipogenicity of berberine mediates anti-inflammtory effect and explored leptin as a candidate mediator of this signaling. We studied this hypothesis by western blot analysis, but our results showed that berberine has no effect on the phosphorylations of STAT-3 and ERK which have important roles on leptin signaling. These results led us to conclude that the anti-inflammatory effect of berberine is not mediated by the inhibition of leptin signal transduction. Moreover, we have found that berberine down-regulates NF-${\kappa}B$ signaling, one of the inflammation-related signaling pathway, through western blot analysis. Taken together, the anti-inflammatory effect of berberine is not mediated by leptin, and berberine induces anti-inflammatory effect independent of leptin signaling.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6507-6512
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• 2015

Background: Vaspin and Retinol binding protein-4 (RBP4) are new adipokines mainly produced by adipose tissue. Considering that medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor, and to date the relationship between serum levels of vaspin and RBP4 with MTC has not been studied, in this matched case-control study we evaluated their possible significance to this tumor type. Materials and Methods: A total of 45 patients with MTC (21 males and 24 females) and 45 healthy persons as a control group (24 males and 21 females) were selected. The two groups were matched for age, sex and body mass index. Serum Vaspin and RBP4 levels were measured by enzyme-linked immunosorbent assay (ELISA) methods in both groups. Also, weight and height were measured and body mass index was calculated too. Results: In total, patients with MTC had significantly higher serum vaspin levels compared to the controls (0.52ng/ml vs. 0.45ng/ml, P=0.0241). However, no significant difference was found in serum RBP4 concentrations between the patients with MTC and the controls ($15.2{\pm}2.55{\mu}g/ml$ versus $15.1{\pm}3.34{\mu}g/ml$, p>0.05). Conclusions: The results of this study demonstrated that serum RBP4 levels in MTC patients are not significantly different from those found in healthy individuals and did not correlate with MTC. On the other hand, higher levels of serum vaspin are associated with an increased risk of MTC. Thus Vaspin may be a novel and promising biomarker for diagnosis or confirmation of MTC in conjunction other specific tumor markers.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.417-424
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• 2014

BACKGROUD/OBEJECTIVES: It is hypothesized that obese people with dyslipidemia is more likely to have increased oxidative stress and decreased antioxidant status, in comparison with the controls who were obese without dyslipidemia. Thus, the aims of the present study were to determine the dietary intakes, plasma adipokines, and antioxidative systems between obese with dyslipidemia and obese without dyslipidemia were investigated. SUBJECTS/METHODS: Female subjects who were between 20 and 55 years old, and whose BMI was 23 or greater were recruited. Subjects who met the criteria of $BMI{\geq}23$, total cholestero ${\geq}200mg/dL$, LDL cholesterol ${\geq}130mg/dL$, and $TG{\geq}110mg/dL$ were categorized Obese with dyslipidemia. Anthropometric measurements and blood biochemical tests were conducted. The diet survey was conducted by a trained dietitian using two days of 24 hour dietary recall. The lipid peroxidation, the plasma total antioxidant capacity (TAC), the activities of antioxidantive enzymes, and various antioxidantive vitamins levels were determined. RESULTS: Plasma adiponectin and leptin levels were also determined. There were no significant differences for age, Body Mass index (BMI), and body fat (%), waist-size between two groups. Obese with dyslipidemia had significantly high levels of total cholesterol, triglyceride, LDL-cholesterol, the ratio of total cholesterol/HDL-C, and the ratio of HDL-C/LDL-C, respectively. Blood alkaline phosphatase level was statistically different between the two groups (P < 0.05). No statistical significance in dietary intake between two groups was shown. In case of obese with dyslipidemia group, the levels of GSH-Px (P < 0.05) and catalase (P < 0.05) as well as adjusted blood retinol (P < 0.05) and tocopherol level (P < 0.05) were significantly low. However, the plasma concentration of leptin was significantly high (P < 0.05). CONCLUSIONS: Obesity with dyslipidemia was shown to have high arthtrogenic index, depleted antioxidant status, and higher blood leptin levels which suggest higher risks of oxidative stress and cardiovascular diseases.

• Nutrition Research and Practice
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• v.9 no.3
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• pp.235-241
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• 2015

BACKGROUND/OBJECTIVES: Doenjang, Korean traditional fermented soybean paste has been reported to have an anti-obesity effect. Because adipose tissue is considered a major source of inflammatory signals, we investigated the protective effects of Doenjang and steamed soybean on oxidative stress and inflammation in adipose tissue of diet-induced obese mice. MATERIALS/METHODS: Male C57BL/6J mice were fed a low fat diet (LF), a high-fat diet (HF), or a high-fat containing Doenjang diet (DJ) or a high-fat containing steamed soybean diet (SS) for 11 weeks. RESULTS: Mice fed a DJ diet showed significantly lower body and adipose tissue weights than those in the HF group. Although no significant differences in adipocyte size and number were observed among the HF diet-fed groups, consumption of Doenjang alleviated the incidence of crown-like structures in adipose tissue. Consistently, we observed significantly reduced mRNA levels of oxidative stress markers (heme oxygenase-1 and $p40^{phox}$), pro-inflammatory adipokines (tumor necrosis factor alpha and macrophage chemoattractant protein-1), macrophage markers (CD68 and CD11c), and a fibrosis marker (transforming growth factor beta 1) by Doenjang consumption. Gene expression of anti-inflammatory adipokine, adiponectin was significantly induced in the DJ group and the SS group compared to the HF group. The anti-oxidative stress and anti-inflammatory effects observed in mice fed an SS diet were not as effective as those in mice fed a DJ diet, suggesting that the bioactive compounds produced during fermentation and aging may be involved in the observed health-beneficial effects of Doenjang. CONCLUSIONS: Doenjang alleviated oxidative stress and restored the dysregulated expression of adipokine genes caused by excess adiposity. Therefore, Doenjang may ameliorate systemic inflammation and oxidative stress in obesity via inhibition of inflammatory signals of adipose tissue.