• Journal of Life Science
• /
• v.30 no.7
• /
• pp.640-650
• /
• 2020

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.

• Journal of Life Science
• /
• v.31 no.10
• /
• pp.954-959
• /
• 2021

Apoptosis is an important mechanism that regulates cellular populations to maintain homeostasis, and the caspases, a family of cysteine proteases, are key mediators of the apoptosis pathway. Caspase-8 is an initiator caspase of the extrinsic apoptotic pathway, which is initiated by extracellular stimuli. Caspase-8 have two conserved domains, N-terminal tandem death effector domains (DED) and C-terminal two catalytic domain, which are important for this extrinsic apoptosis pathway. In extrinsic apoptosis pathway, death receptors which members of TNF superfamily are activated by binding of death receptor specific ligands from cell outside. After the activated death receptors recruit adaptor protein Fas-associated death domain protein (FADD), death domains (DD) of death receptor and FADD bind to each other and FADD combined with death receptor recruits procaspase-8, a precursor form of caspase-8. The DED of FADD and procaspase-8 bind to one another and FADD-bound procaspase-8 is activated by cleavage of the prodomain. This death receptor-FADD-caspase-8 complex called death inducing signaling complex (DISC). Cellular FLICE-inhibitory proteins (c-FLIPs) regulate caspase-8 activation by acting both anti- and pro-apoptotically, and caspase-8 activation initiates the activation of executioner caspases such as caspase-3. Finally activated executioner caspases complete the apoptosis by acting critically DNA degradation, nuclear condensation, plasma membrane blebbing, and the proteolysis of certain caspase substrates.

• Journal of the Daesoon Academy of Sciences
• /
• v.47
• /
• pp.39-63
• /
• 2023

Modern medical science tends to categorize addiction as a kind of disease, but a Taoist world-view would not consider addiction to be a disease. Taoists do not have a concept of addiction as an eternal substance. Within the Taoist world-view, human beings are meant to live in harmony with the transformative cycles of nature. Human beings achieve self-realization through balancing themselves with nature. This is what is meant by Self-Realization in Harmony with Nature. There is no disease known as addiction when one's life is in harmony with nature. There are two main principles in the Taoist medical worldview. First, is the theory of correspondences. This theory of correspondences is the foundational to Taoism's value-neutral world-view wherein humans are seen as working together with Heaven and Earth in correlative relationships to create harmonious societies. Second, is the principle of harmony and balance in the Universe. One creature can be in harmony with other creatures and learn to appreciate the interconnectedness of all living beings. Survival of the forest is vital to the survival of natural harmony, balance, morality, and environment. The vitality of the human body depends on the movement of Qi energy. According to the principles of Korean traditional medicine, all human problems stem from the mind. There is no madness, no illness, no tempting fate, and even no death outside of what stems from the mind. Within the human body, there are two principles behind energy systems: harmony and balance. When human beings achieve the state of homeostasis, they obtain Qi flows which are associated with the various organs. In doing so, they can always maintain a healthy state of life in accordance with the cosmic rhythm. Taoist philosophy contains advice that prevents addiction. Empty your mind of all thought. Let your heart be peaceful. Finally, all worries are washed away by the cosmic wave.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.6
• /
• pp.836-845
• /
• 1999

Background : Obesity is present in the majority of adult patients with obstructive sleep apnea(OSA) and is considered to be a major risk factor for its development. A reduction in body weight has been associated with substantial improvement in the severity of apnea. However, a variety of treatment strategies for obesity have yielded limited sucess. This study was done to determine resting energy expenditure(REE) in patients with obstructive sleep apnea and the correlation between the severity of sleep apnea and REE, and to investigate whether leptin influences REE and correlated with the severity of sleep apnea in 39 patients with OSA and 45 controls matched for obesity. Method : Overnight polysomnography was performed on all subjects using standard techniques. Measurements of REE were made using a Sensormedic Vmax 229 and a canopy system. Serum leptin concentration was measured by human leptin RIA kit of LINCO Research INC. Results : REE was greater in patients with OSA compared with controls, but there was no difference between the two groups on REE%. And also there was no significant correlation between anthropometric data, polysomnographic data and REE%. Serum leptin was linearly related to body mass index(BMI), apnea index, apnea hypopnea index and lowest arterial oxygen saturation($SaO_2$) but not related to REE%. Conclusion : This study suggests the followings. Firstly patients patients with sleep apnea have a pattern of obesity characterized by energy homeostasis at an elevated body weight set-point. In order to achieve a lower body weight in these patients, it may be necessary to increase energy expenditure by increasing physical activity. Secondly leptin level was not correlated with REE, suggesting that leptin may predominantly regulate body fat by altering eating behavior rather than calorigenesis. Lastly leptin level was significantly correlated with the severity of sleep apnea. These elevated level of leptin in patients of sleep apnea may be related to the obesity, however it needs further studies to determine the relationship between the severity of sleep apnea and serum leptin.

• Journal of Life Science
• /
• v.28 no.3
• /
• pp.284-292
• /
• 2018

The melanin-concentrating hormone (MCH), a cyclic hypothalamic peptide composed of 17 amino acids, was initially identified in chum salmon (Oncorhynchus keta) as a regulator of pigmentation. Mammalian MCHs are cyclic hypothalamic peptides composed of 19 amino acids that regulate food intake and energy homeostasis. The present study examined not only MCH expression of different tissues but also the melanohore aggregation and intracellular $Ca^{2+}$ influx of fMCH and the other MCH. Real-time qPCR showed that MCH expressed specially in the brain, gonad, and ovary, and expression of MCH was observed during the developmental stages. In the application of synthetic fMCH and both types of synthetic fMCH, dN-fMCH and dC-fMCH, scale melanophore induced significant changes in aggregation activity with various concentrations of MCH. Also, compared to hMCH and sMCH, fMCH exhibited a 36~99.85% increase in relative potency (%), whereas aggregation of dN-fMCH and dC-fMCH remained in a high concentration. However, dispersion was induced rapidly according to be low concentration of dN-fMCH and dC-fMCH. We show that fMCH and its derivates were bound human MCHR1 and rat MCHR expressed in HEK293T cells with nano-molar affinity and are likely to be ligand-induced to mobilize intracellular $Ca^{2+}$. These results may provide new ligands for binding assay with MCHew ligands, as a structure similar to the mammalian MCH structure was discovered in fish. Once the fMCH receptor system is in place, it can be compared to the MCH system of mammals in terms of MCH function.

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

• Nutrition Research and Practice
• /
• v.8 no.2
• /
• pp.177-182
• /
• 2014

BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with energy homeostasis. We investigated whether aged garlic extract (AGE) and exercise training intervention could improve body weight, insulin sensitivity, skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats were fed a ND (normal diet, n=5) or HFD (n=28) for 6 weeks. After 6 weeks, all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n=5), HFD (high-fat diet, n=7), HFDA (high-fat diet + aged garlic extract, n=7), HFDE (high-fat diet + exercise, n=7), and HFDEA (high-fat diet + exercise + aged garlic extract, n=7). Exercise groups performed treadmill exercises for 15-60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for 4 weeks. RESULTS: Significant decreases in body weight were observed in the ND, HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention affected the masses of the gastrocnemius muscle or liver. There were no significant differences in glucose levels across the groups. The homeostatic model assessments of insulin resistance were significantly higher in the HFD group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or exercise in obese rats. AGE supplementation and exercise training did not affect skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin sensitivity in obese rats. CONCLUSION: Our results suggest that the protection against HFD-induced increases in body fat/weight and insulin resistance that are provided by AGE supplementation and exercise training may not be mediated by the regulation of FNDC-5 or irisin.

• Journal of Nutrition and Health
• /
• v.46 no.1
• /
• pp.61-71
• /
• 2013

The aim of this study was to examine the relationship between dietary variables and the prevalence of insulin resistance (IR) in middle-aged Korean adults using data from the 2007-2009 Korea National Health and Nutrition Examination Survey. Because IR is closely linked with metabolic syndrome, subjects were divided into three groups according to symptoms of metabolic syndrome: the 'Normal group' without any symptoms, the 'Risk group' with one or two symptoms, and the Metabolic syndrome (MetS) group' with three or more symptoms. Subjects between the ages of 30 and 65 years with no prior diagnosis or treatment for diabetes, hypertension, or dyslipidemia were selected. The number of subjects per group was as follows: 2,085 adults in the Normal group, 3,699 adults in the Risk group, and 1,160 adults in the MetS group. Metabolic syndrome was defined according to Adult Treatment Panel III criteria with modified waist circumference cutoff values (men ${\geq}$ 90 cm, women ${\geq}$ 85 cm). Subjects with HOMA-IR > 2.0 were classified as IR. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated using the following formula: (fasting plasma glucose ${\times}$ fasting plasma insulin)/22.5. Nutrients and food groups intake were obtained from a single 24-hour recall. Subjects with IR in the Normal group were more obese and less physically active than non-IR subjects. In the MetS group, subjects with IR were more obese and had a lower prevalence of smoking and drinking, compared with non-IR subjects. Men with IR in the Normal group had a tendency to consume more oils and sugars than non-IR men, while women with IR in the same group had higher intake of carbohydrate, dietary glycemic index, and dietary glycemic load than non-IR women. Women with IR in the Risk group had lower energy intake but higher intake of oils and sugars than non-IR women. In the MetS group, consumption of fruits was higher in subjects with IR than in non-IR subjects. In conclusion, findings of this study suggest that dietary carbohydrate intake, including glycemic index, may be associated with IR in healthy women. Further research in prospective cohort studies in order to examine the effects of dietary carbohydrate on IR incidence will be necessary.

• Molecular & Cellular Toxicology
• /
• v.5 no.4
• /
• pp.298-303
• /
• 2009

(-)-Epigallocatechin-3-gallate (EGCG), a major flavonoid in green tea has multiple health benefits including chemoprevention, anti-inflammatory, anti-diabetic, and anti-obesity effects. In connection with these effects, EGCG can be a candidate to help the treatment of metabolic diseases. Metformin is a widely used anti-diabetic drug regulating cellular energy homeostasis via AMP-activated protein kinase (AMPK) activation. Therefore, the combination of metformin with EGCG may have additive or synergistic effects on treatment of type 2 diabetes. Nevertheless, there is no report for the pharmacokinetic and/or pharmacodynamic interaction of EGCG with metformin. Here, we evaluated the pharmacokinetic and pharmacodynamic interaction between metformin and EGCG in rats. Pharmacokinetics parameters of metformin were measured after oral administration of metformin in rats pre-treated with EGCG (10 mg/kg) or saline for 7 days. The results showed that there is no significant difference in pharmacokinetic parameters between saline control and EGCG-treated group. In addition, the hepatic AMPK activation by metformin in EGCG-treated rats was also similar to the control. The lack of additive effects of EGCG on AMPK activation or intracellular uptake of metformin was also evaluated in cells in the presence or absence of EGCG. Treatment of HepG2 cells with EGCG inhibited the metformin-induced AMPK activation. Combined results suggested that EGCG has no effect on the pharmacokinetics of metformin but may contribute to metformin action.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.43 no.5
• /
• pp.763-771
• /
• 2014

The objective of this study was to assess the relationship between dietary sodium intake and prevalence of abdominal obesity in Korean adults. We used data from the Korea National Health and Nutrition Examination Survey V-1 and analyzed data on 4,475 Koreans (${\geq}30$ years old). Subjects were divided into three groups according to fasting plasma glucose (FPG): 1) normal (FPG <100 mg/dL), 2) pre-diabetes ($100mg/dL{\leq}FPG{\leq}125mg/dL$), and 3) diabetes (FPG ${\geq}126mg/dL$ or subjects diagnosed with diabetes). The subjects in each category were stratified by dietary sodium intake as well as index of abdominal obesity. We found that dietary sodium intake was positively correlated with waist circumference (WC) (P=0.002) and was particularly high in the pre-diabetes group. In multiple logistic regression analysis, the normal and diabetes groups showed no association between dietary sodium intake and WC, whereas the pre-diabetes group with a high sodium intake exhibited a significant association (odds ratio (OR)=1.479, P=0.029) between dietary sodium intake and WC. Further, the OR for abdominal obesity in the high sodium intake group with pre-diabetes was 1.590 after adjusting for age and sex (P=0.012). In addition, the ORs for the prevalence of abdominal obesity with fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance were significantly higher in the pre-diabetes group with high sodium intake compared with low sodium intake. Moreover, these associations were significant even after adjusting for confounding variables (model 2: age and sex; model 3: age, sex, and total energy intake). Our results suggest a strong association between sodium intake and abdominal obesity in pre-diabetes Korean adults.