• Journal of Ginseng Research
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• v.47 no.3
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• pp.400-407
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• 2023

Background: Rb3 is a ginsenoside with anti-inflammatory properties in many cell types and has been reported to attenuate inflammation-related metabolic diseases such as insulin resistance, nonalcoholic fatty liver disease, and cardiovascular disease. However, the effect of Rb3 on podocyte apoptosis under hyperlipidemic conditions, which contributes to the development of obesity-mediated renal disease, remains unclear. In the current study, we aimed to investigate the effect of Rb3 on podocyte apoptosis in the presence of palmitate and explore its underlying molecular mechanisms. Methods: Human podocytes (CIHP-1 cells) were exposed to Rb3 in the presence of palmitate as a model of hyperlipidemia. Cell viability was assessed by MTT assay. The effects of Rb3 on the expression of various proteins were analyzed by Western blotting. Apoptosis levels were determined by MTT assay, caspase 3 activity assay, and cleaved caspase 3 expression. Results: We found that Rb3 treatment alleviated the impairment of cell viability and increased caspase 3 activity as well as inflammatory markers in palmitate-treated podocytes. Treatment with Rb3 dosedependently increased PPARδ and SIRT6 expression. Knockdown of PPARδ or SIRT6 reduced the effects of Rb3 on apoptosis as well as inflammation and oxidative stress in cultured podocytes. Conclusions: The current results suggest that Rb3 alleviates inflammation and oxidative stress via PPARδ-or SIRT6-mediated signaling, thereby attenuating apoptosis in podocytes in the presence of palmitate. The present study provides Rb3 as an effective strategy for treating obesity-mediated renal injury.

• ALGAE
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• v.38 no.1
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• pp.81-92
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• 2023

Obesity-induced inflammation is crucial in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we investigated the effects of the Gracilaria chorda (GC) on lipid accumulation and obesity-induced inflammatory changes or glucose homeostasis in cell models (3T3-L1 adipocytes and RAW 264.7 macrophages). Samples of GC were extracted using solvents (water, methanol, and ethanol) and subcritical water (SW) at different temperatures (90, 150, and 210℃). The total phenolic content of GCSW extract at 210℃ (GCSW210) showed the highest content compared to others, and GCSW210 highly inhibited lipid accumulation and significantly reduced gene expressions of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α, sterol regulatory element-binding protein-1c, and fatty acid synthase in 3T3-L1 adipocytes. In addition, GCSW210 effectively downregulated the pro-inflammatory cytokine regulator pathways in RAW 264.7 macrophages, including mitogen-activated protein kinase, signal transducers and activators of transcription and nuclear factor-κB. In co-culture of 3T3-L1 adipocytes and RAW 264.7 macrophages, GCSW210 significantly reduced nitric oxide production and interleukin-6 levels, and improved glucose uptake with dose-dependent manner. These findings suggest that GCSW210 improves glucose metabolism by attenuating obesity-induced inflammation in adipocytes, which may be used as a possible treatment option for managing obesity and associated metabolic disorders.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.324-331
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• 2015

Thyroid hormones are essential for cellular energy homeostasis and regulation by interacting with the sympathetic nervous system. This study was conducted to investigate the relationship between thyroid hormone and risk factors of metabolic syndrome for medical checkups of male patients. The study subjects were 12,250 males between 20~80 years old who visited the hospital for a health check-up at one General Hospital in Gyeonggi-do during the period of January 2011 to December 2013. According to the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), the metabolic syndrome criteria is defined as the presence of 3 or more risk factors. FT4 was lower in the metabolic syndrome group than in the normal group (p<0.001). The level of FT4 decreased as the levels of abdominal obesity (p=0.001), hypertriglyceridemia (p<0.001), blood pressure (p=0.005) and blood glucose (p=0.005) increased. The TSH level increased hypertriglyceridemia (p=0.047). FT4 had an influence on the waist circumference and triglyceride (p<0.001). HbA1c, insulin, HOMA-IR, hs-CRP were higher in the lowest quartile than in the highest quartile (p<0.001). FT4 had effects on the waist circumference and triglyceride, but TSH had no effect on metabolic syndrome risk factors. The metabolic syndrome was lower in the highest quartile of FT4 than in its lowest quartile.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.213-220
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• 2016

Mast cells are primary mediators of allergic inflammation. Beta-1,3-glucan (BG) protects against infection and shock by activating immune cells. Activation of the BG receptor induces an increase in intracellular $Ca^{2+}$, which may induce exocytosis. However, little is known about the precise mechanisms underlying BG activation of immune cells and the possible role of mitochondria in this process. The present study examined whether BG induced mast cell degranulation, and evaluated the role of calcium transients during mast cell activation. Our investigation focused on the role of the mitochondrial calcium uniporter (MCU) in BG-induced degranulation. Black mouse (C57) bone marrow-derived mast cells were stimulated with $0.5{\mu}g/ml$ BG, $100{\mu}g/ml$ peptidoglycan (PGN), or $10{\mu}M$ A23187 (calcium ionophore), and dynamic changes in cytosolic and mitochondrial calcium and membrane potential were monitored. BG-induced mast cell degranulation occurred in a time-dependent manner, and was significantly reduced under calcium-free conditions. Ruthenium red, a mitochondrial $Ca^{2+}$ uniporter blocker, significantly reduced mast cell degranulation induced by BG, PGN, and A23187. These results suggest that the mitochondrial $Ca^{2+}$ uniporter has an important regulatory role in BG-induced mast cell degranulation.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.531-546
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• 2017

Activation of Toll-like receptor-4 (TLR-4) in articular chondrocytes increases the catabolic compartment and leads to matrix degradation during the development of osteoarthritis. In this study, we determined the proteomic and genomic alterations in human chondrocytes during lipopolysaccharide (LPS)-induced inflammation to elucidate the underlying mechanisms and consequences of TLR-4 activation. Human chondrocytes were cultured with LPS for 12, 24, and 36 h to induce TLR-4 activation. The TLR-4-induced inflammatory response was confirmed by real-time PCR analysis of increased interleukin-1 beta ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis factor alpha ($TNF-{\alpha}$) expression levels. In TLR-4-activated chondrocytes, proteomic changes were determined by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-mass spectroscopy analysis, and genomic changes were determined by microarray and gene ontology analyses. Proteomics analysis identified 26 proteins with significantly altered expression levels; these proteins were related to the cytoskeleton and oxidative stress responses. Gene ontology analysis indicated that LPS treatment altered specific functional pathways including 'chemotaxis', 'hematopoietic organ development', 'positive regulation of cell proliferation', and 'regulation of cytokine biosynthetic process'. Nine of the 26 identified proteins displayed the same increased expression patterns in both proteomics and genomics analyses. Western blot analysis confirmed the LPS-induced increases in expression levels of lamin A/C and annexins 4/5/6. In conclusion, this study identified the time-dependent genomic, proteomic, and functional pathway alterations that occur in chondrocytes during LPS-induced TLR-4 activation. These results provide valuable new insights into the underlying mechanisms that control the development and progression of osteoarthritis.

• Molecules and Cells
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• v.37 no.6
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• pp.441-448
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• 2014

Inflammasomes are specialized signaling platforms critical for the regulation of innate immune and inflammatory responses. Various NLR family members (i.e., NLRP1, NLRP3, and IPAF) as well as the PYHIN family member AIM2 can form inflammasome complexes. These multiprotein complexes activate inflammatory caspases (i.e., caspase-1) which in turn catalyze the maturation of select pro-inflammatory cytokines, including interleukin (IL)-$1{\beta}$ and IL-18. Activation of the NLRP3 inflammasome typically requires two initiating signals. Toll-like receptor (TLR) and NOD-like receptor (NLR) agonists activate the transcription of pro-inflammatory cytokine genes through an NF-${\kappa}B$-dependent priming signal. Following exposure to extracellular ATP, stimulation of the P2X purinoreceptor-7 ($P2X_7R$), which results in $K^+$ efflux, is required as a second signal for NLRP3 inflammasome formation. Alternative models for NLRP3 activation involve lysosomal destabilization and phagocytic NADPH oxidase and /or mitochondria-dependent reactive oxygen species (ROS) production. In this review we examine regulatory mechanisms that activate the NLRP3 inflammasome pathway. Furthermore, we discuss the potential roles of NLRP3 in metabolic and cognitive diseases, including obesity, type 2 diabetes mellitus, Alzheimer's disease, and major depressive disorder. Novel therapeutics involving inflammasome activation may result in possible clinical applications in the near future.

• Korean Journal of Health Education and Promotion
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• v.26 no.2
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• pp.149-155
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• 2009

Metabolically obese but normal weight(MONW) syndrome is characterized, with potentially increased risks for development of the insulin resistance or metabolic syndrome despite their normal body mass index(BMI) < 25 kg/m2. Such characteristics could confer upon MONW individuals a type 2 diabetes mellitus and cardiovascular diseases(CVD) risk however, research on MONW is scarce. MONW individuals have metabolic disturbances typical of obese persons and are identified by having a high amount of visceral fat, a low BMI, a high fat mass, a low lean body mass, low insulin sensitivity, and high triglyceride concentrations. The purpose of this study is to review several markers as potential modulators in individuals displaying the "MONW". Body fat appears to be functionally comparable with a dynamic endocrine organ, producing and secreting various adipocy tokines, such as leptin, adiponectin, CRP, tumor necrosis factor(TNF-), interleukin(IL)-6, all of which play an important role in the onset of cardiovascular disease, and insulin resistance. Otherwise, physical activity and a lower inflammation state might be helped to reduce the number of persons at risk of diabetes, CVD complications, or premature mortality. We should provide a method to optimal treatments resolving the emerging public health problem to prevention of MONW by providing guideline for physical activity as an optimal treatment for the MONW Korean. Furthermore we expect to develop a new strategy to manage MONW Korean in this society in terms of reducing medical costs and enhancing public health care for uprising population with MONW.

• Archives of Obesity and Metabolism
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• v.1 no.2
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• pp.66-73
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• 2022

Obesity is an increasing public health and medical issue worldwide. It has been associated with several comorbidities, including diabetes, cardiovascular disease, stroke, and cancer. Chronic kidney disease (CKD) is another important comorbidity of obesity. Other major causes of CKD include hypertension and diabetes. However, the association between obesity and CKD is often overlooked. Among patients with CKD, patients with obesity were more vulnerable to have rapid kidney function decline than that of those with normal weight. Additionally, CKD is more prevalent among patients with obesity. These aggravations are induced through multiple mechanisms, specifically metabolic impairment of obesity and mechanical burden because of increasing intraabdominal renal pressure. Furthermore, the inflammation and lipotoxicity, caused by obesity, are critical in the CKD aggravation in patients with obesity. To prevent this, all adult patients with obesity are tested for CKD. The workup includes the estimated glomerular filtration rate and regular follow-up. Step-wise management is required for patients with obesity with CKD. Prompt reduction and management of obesity effectively delay CKD progression among patients with obesity and CKD. Therefore, weight loss is a core management for patients with obesity and CKD. Based on several studies, this article focused on the association between CKD and obesity, as well as the diagnosis and weight management of patients with obesity and CKD.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.870-882
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• 2023

BACKGROUND/OBJECTIVES: Obesity is a major risk factor for metabolic syndrome, a global public health problem. Mentha canadensis (MA), a traditional phytomedicine and dietary herb used for centuries, was the focus of this study to investigate its effects on obesity. MATERIALS/METHODS: Thirty-five male C57BL/6J mice were randomly divided into 2 groups and fed either a normal diet (ND, n = 10) or a high-fat diet (HFD, n = 25) for 4 weeks to induce obesity. After the obesity induction period, the HFD-fed mice were randomly separated into 2 groups: one group continued to be fed HFD (n = 15, HFD group), while the other group was fed HFD with 1.5% (w/w) MA ethanol extract (n = 10, MA group) for 13 weeks. RESULTS: The results showed that body and white adipose tissue (WAT) weights were significantly decreased in the MA-supplemented group compared to the HFD group. Additionally, MA supplementation enhanced energy expenditure, leading to improvements in plasma lipids, cytokines, hepatic steatosis, and fecal lipids. Furthermore, MA supplementation regulated lipid-metabolism-related enzyme activity and gene expression, thereby suppressing lipid accumulation in the WAT and liver. CONCLUSIONS: These findings indicate that MA has the potential to improve diet-induced obesity and its associated complications, including adiposity, dyslipidemia, hepatic steatosis, and inflammation.

• Korean Journal of Food Science and Technology
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• v.44 no.5
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• pp.526-531
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• 2012

Olive oil is widely consumed in Korea, and is a representative fat source in the Mediterranean diet, known to be effective in the prevention of coronary artery disease. In addition, diverse functionalities have been reported, such as anti-cancer, anti-oxidation, and anti-inflammation effects. In this review, the status of production and variety were investigated with respect to the functionalities of olive oil. The main functional constituents of olive oil are oleic acid, known to improve blood cholesterol, and the minor constituents are polyphenol, tocopherol, squalene, and phospholipid, the concentrations of which can be used to distinguish pressed from refined olive oil. A number of studies of the functionality of olive oil have dealt with the minor constituents, and the beneficial functionalities, such as anti-oxidation, anti-inflammation, and improving blood circulation have been reported. This review intensively investigates the functionalities and the responsible components, and suggests that continual studies on olive oil are necessary for the prevention of various metabolic diseases.