• Title/Summary/Keyword: Insulin Resistance

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Phenotype Changes in Immune Cell Activation in Obesity (비만 환경 내 면역세포 활성화 표현형의 변화)

  • Ju-Hwi Park;Ju-Ock Nam
    • Journal of Life Science
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    • v.33 no.3
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    • pp.295-303
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    • 2023
  • Immune and metabolic systems are important factors in maintaining homeostasis. Immune response and metabolic regulation are highly associated, so, when the normal metabolism is disturbed, the immune response changed followed the metabolic diseases occur. Likewise, obesity is highly related to immune response. Obesity, which is caused by an imbalance in energy metabolism, is associated with metabolic diseases, such as insulin resistance, type 2 diabetes, fatty liver diseases, atherosclerosis and hypertension. As known, obesity is characterized in chronic low-grade inflammation. In obesity, the microenvironment of immune cells became inflammatory by the unique activation phenotypes of immune cells such as macrophage, natural killer cell, T cell. Also, the immune cells interact each other in cellular or cytokine mechanisms, which intensify the obesity-induced inflammatory response. This phenomenon suggests the possibility of regulating the activation of immune cells as a pharmacological therapeutic strategy for obesity in addition to the common pharmacological treatment of obesity which is aimed at inhibiting enzymes such as pancreatic lipase and α-amylase or inhibiting differentiation of preadipocytes. In this review, we summarize the activation phenotypes of macrophage, natural killer cell and T cell, and their aspects in obesity. We also summarize the pharmacological substances that alleviates obesity by regulating the activation of immune cells.

Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD

  • Zehong Yang;Yuanyuan Yu ;Nannan Sun;Limian Zhou;Dong Zhang;HaiXin Chen ;Wei Miao ;Weihang Gao ;Canyang Zhang ;Changhui Liu ;Xiaoying Yang ;Xiaojie Wu ;Yong Gao
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.376-384
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    • 2023
  • Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

Active Aging: Roles of Physical Activity and Immunity (건강한 노후 : 운동활동과 면역반응을 중심으로)

  • Park, Chan Ho;Kim, Ji-Seok;Kwak, Yi Sub
    • Journal of Life Science
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    • v.28 no.5
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    • pp.621-626
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    • 2018
  • We introduced the physiological responses of aging, active aging and also suggest the impact of physical exercise on body health status and elderly immunity. In this purpose, we searched the Pub Med data base for the articles (include our experimental papers) and review papers having the terms 'Aging', 'Active aging' and 'Physical activity and elderly' in the title, published from 1999 until 2018. The results were as follows: Exercise training has been extensively studied about the reduction of inflammation, oxidative stress, disease, and aging in syndrome X patients and elderly. Combined and aerobic or resistance exercise training could reduce obesity, insulin resistance, type 2 diabetes and hypertension. Exercise training has been extensively studied in cancer settings as part of prevention or treatment strategies. From this research, regular exercise has the potential to target tumor growth through regulation of inflammation and immune responses such as lactate clearance, NK cell activation (innate immunity), activation of cytotoxic immune cells, T cell activation (adaptive immunity), and immune surveillance. However, Endurance physical activity not only induces thermogenesis and diverse sports injuries but also elicits mobilization and functional enhancement of monocytes, neutrophils (which is caused by the cytokine changes such as TNF-alpha, IL-1) whereas it suppresses cell mediated immunity causing to increased susceptibility to inflammation and infections like cough and URTIs (upper respiratory track infections) in young and especially in elderly people. Therefore, Strategies to prevent physical fatigue, sports injuries include avoid overtraining, Adequate recovery and various type of rest during and after physical activity and assuring adequate nutrition supplementation such as glutamine, vitamin B, vitamin C, carbohydrate, ion or berry-contain sports beverages is helpful in physically active elderly.

Metabolic syndrome in the overweight and obese adolescents and the impact of obesity on the cardiovascular system (과체중과 비만 청소년에서 대사증후군과 비만이 심혈관에 미치는 영향)

  • Hong, Young Mi;Song, Young Whan;Kim, Hae Soon;Park, Hae Sook;Min, Jung Hae;Jung, Jo Won;Kim, Nam Su;Noh, Chung Il
    • Clinical and Experimental Pediatrics
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    • v.52 no.10
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    • pp.1109-1118
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    • 2009
  • Purpose : Metabolic syndrome (MS), characterized by obesity and insulin resistance, elicits risk factors such as hyperlipidemia, hypertension, and glucose intolerance with additive effects on atherosclerosis, leading to cardiovascular diseases. The purposes of this study were to evaluate the prevalence of MS among overweight and obese adolescents and to investigate the impact of obesity on the cardiovascular system. Methods : In all, 684 adolescents were included in the study. Blood pressure, body mass index (BMI), fasting blood glucose, total cholesterol, triglyceride, low-density-lipoprotein (LDL)-cholesterol, high-density-lipoprotein (HDL)-cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and high-sensitive C-reactive protein (hs-CRP) were measured in the patients with a BMI of >85 percentile. Brachial-ankle pulse wave velocity (BaPWV) and ankle brachial index were measured using Vascular Profiler (VP)-1000. Results : MS was confirmed in 19.5% of the overweight and obese adolescents and 50.8% of the obese adolescents. The systolic and diastolic blood pressure, height, weight, fat mass, %fat, BMI, obesity index, and waist circumference were higher in the overweight and obese adolescents with MS. Moreover, the triglyceride, AST, ALT, and hs-CRP levels were higher, whereas HDL-cholesterol level was significantly lower in this group. The overweight and obese adolescents with MS showed shorter diastolic and systolic times, higher heart rate and BaPWV, and longer E-wave deceleration time by echocardiography. Conclusion : Overweight and obese adolescents showed characteristic MS features such as hypertension and hyperlipidemia. Thus, obese adolescents predisposed to MS should be provided early treatment for obesity.

Effect of Conjugated Linoleic Acid on Nuclear Factor-${\kappa}B$ Activation and Tumor Necrosis Factor-${\alpha}$ Production in RAW 264.7 Cells Exposed to High Concentration of Glucose (고농도의 당에 노출된 RAW 264.7 세포에서 conjugated linoleic acid의 TNF-${\alpha}$ 생산과 NF-${\kappa}B$의 활성 효과)

  • Lee, Minji;Kang, Byeong-Teck;Kang, Ji-Houn;Yang, Mhan-Pyo
    • Journal of Veterinary Clinics
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    • v.29 no.5
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    • pp.361-367
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    • 2012
  • Diabetes-related complications in human and veterinary medicine have been shown to be associated with hyperglycemia-induced inflammation. It has been recently suggested that the onset of insulin resistance may be caused by over-production of inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$ from immune cells. Conjugated linoleic acid (CLA) regulates inflammatory response through modulation of TNF-${\alpha}$ expression. The objective of this study was to examine the effect of CLA on nuclear factor kappaB (NF-${\kappa}B$) p65 binding activity, inhibitory kappaB ($I{\kappa}B$)-${\alpha}$ expression, and TNF-${\alpha}$ production from high glucose-treated RAW 264.7 cells. CLA was added to RAW cells that had been previously cultured with low or high concentration of glucose. The levels of TNF-${\alpha}$ protein in the culture supernatant of RAW cells exposed to high concentrations of glucose were higher than those of cells exposed to low concentrations of glucose. The treatment with the high concentration of glucose in RAW cells increased levels of NF-${\kappa}B$ p65 binding activity and the decreased $I{\kappa}B-{\alpha}$ expression when compared with those of low glucose. The treatments in combination with CLA and glucose (low and high) glucose in RAW cells increased TNF-${\alpha}$ production when compared with that glucose alone. These treatments with CLA increased TNF-${\alpha}$ production in high glucose-treated RAW cells than those with low glucose. These treatments of CLA also showed higher NF-${\kappa}B$ p65 binding activity and lower $I{\kappa}B-{\alpha}$ expression in high glucose than those in low glucose condition. This suggests that CLA can increase NF-${\kappa}B$ p65 binding activity and TNF-${\alpha}$ production from high glucose-treated RAW 264.7 cells and is likely to promote hyperglycemia-induced inflammation.

Anti-obesity Effects of Peucedanum japonicum Thunberg L. on 3T3-L1 Cells and High-fat Diet-induced Obese Mice (식방풍잎(Peucedanum japonicum Thunberg L.)의 물추출물이 3T3-L1 세포와 고지방식이로 유도된 마우스에서 항비만 효과)

  • Jung, Ho-Kyung;Sim, Mi-Ok;Jang, Ji-Hun;Kim, Tae-Muk;An, Byeong-Kwan;Kim, Min-Suk;Jung, Won Seok
    • Korean Journal of Plant Resources
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    • v.29 no.1
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    • pp.1-10
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    • 2016
  • Obesity is a pro-inflammatory state that contributes to the development of metabolic disorders such as hyperlipidemia, insulin resistance, type 2 diabetes, non-alcoholic fatty liver, and cardiovascular disease. In this study, we evaluated the inhibition of adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice by Peucedanum japonicum Thunberg L. water extract (PJT). Lipid accumulation measurement indicates that PJT markedly inhibited adipogenesis in a dose-dependent manner. RT-PCR results demonstrated that the mRNA expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α (C/EBPα) in 3T3-L1 cells were significantly down-regulated by PJT treatment. Oral administration of PJT (100, 300, and 500 ㎎/㎏, b.w/daily for 4 weeks) was conducted in high-fat diet induced obese mice and C57BL/6 mice. The PJT-administered group of HFD-induced mice had a lower body weight gain, along with decreased serum levels of glucose, triglycerides, and total cholesterol compared with the control mice, however, the HDL-cholesterol/total cholesterol ratio was increased. Furthermore, the elevated mRNA expression levels of adipogenesis related genes in the white adipose tissue of obese mice were significantly suppressed by PJT. These results indicate that PJT exhibits anti-obesity effects in obese mice by decreasing in serum lipid levels and lipogenesis related gene.

Effects of Obesity on Pulmonary Functions in Children (소아에서 비만이 운동 전후의 폐활량에 미치는 영향)

  • Park, Seok Won;Kim, Hwang Min;Kim, Jong Soo;Cha, Jae Kuk;Lee, Hae Ran
    • Clinical and Experimental Pediatrics
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    • v.45 no.5
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    • pp.588-595
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    • 2002
  • Purpose : The incidence of obesity has increased in Korea recently. Obesity leads to higher risks of hypertension, hyperlipidemia and insulin resistance. It also leads to risks of respiratory complications. This study was performed to see the effects of obesity on children's pulmonary functions and on developed bronchospasm after exercise loading according to their obesity degrees. Methods : 257 obese children and 150 non-obese children were enrolled. Obese children were divided into 3 groups by the obesity degrees. Pre- and post-exercise loading $FEV_1$(forced expiratory volume at one second), FVC(forced vital capacity) and PEFR(peak expiratory flow rate) were checked in all subjects. The percent predicted values of each parameter was compared according to obesity degrees and the differences between pre-exercise and post-exercise values. Results : The percent predicted value of $FEV_1$, FVC decreased only in the severe obesity group compared with those in the control group. However percent predicted PEFR declined according to obesity degrees. The percent predicted value of $FEV_1$, FVC and PEFR after exercise loading were much lower than those before exercise loading in all groups. Conclusion : As the degree of obesity was higher, the percent predicted value of pulmonary function was lower. And after exercise loading, as the degree of obesity was higher, the reduction of percent predicted value of pulmonary function was larger. Therefore the pulmonary function in obese children must be observed carefully. Further studies on the effects of pulmonary functions in obese children are necessary.