Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on apigenin analyzed its effect on ...histamine release in the 1950s. Since then, anti-mutation and antitumor properties of apigenin have been widely reported. In the present study, we evaluated the apigenin-mediated amelioration of skin disease and investigated its applicability as a functional ingredient, especially in cosmetics. The effect of apigenin on RAW264.7 (murine macrophage), RBL-2H3 (rat basophilic leukemia), and HaCaT (human immortalized keratinocyte) cells were analyzed. Apigenin (100 μM) significantly inhibited nitric oxide (NO) production, cytokine expression (interleukin (IL)-1β, IL6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase iNOS), and phosphorylation of mitogen-activated protein kinase (MAPK) signal molecules, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) in RAW264.7 cells. Apigenin (30 M) also inhibited the phosphorylation of signaling molecules (Lyn, Syk, phospholipase Cγ1, ERK, and JNK) and the expression of high-affinity IgE receptor FcεRIα and cytokines (tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-6, IL-13, and COX-2) that are known to induce inflammation and allergic responses in RBL-2H3 cells. Further, apigenin (20 μM) significantly induced the expression of filaggrin, loricrin, aquaporin-3, hyaluronic acid, hyaluronic acid synthase (HAS)-1, HAS-2, and HAS-3 in HaCaT cells that are the main components of the physical barrier of the skin. Moreover, it promoted the expression of human β-defensin (HBD)-1, HBD-2, HBD-3, and cathelicidin (LL-37) in HaCaT cells. These antimicrobial peptides are known to play an important role in the skin as chemical barriers. Apigenin significantly suppressed the inflammatory and allergic responses of RAW264.7 and RBL cells, respectively, and would, therefore, serve as a potential prophylactic and therapeutic agent for immune-related diseases. Apigenin could also be used to improve the functions of the physical and chemical skin barriers and to alleviate psoriasis, acne, and atopic dermatitis.
Obesity is an increasing public health concern worldwide. According to the latest Organization for Economic Co-operation and Development (OECD) report (2014), the incidence of child obesity in Korea ...has exceeded the OECD average. To better understand and control this condition, the present study examined the composition of the gut microbial community in normal and obese adolescents. Fecal samples were collected from 67 obese (body mass index BMI ≥ 30 kg/m2, or ≥ 99th BMI percentile) and 67 normal (BMI < 25 kg/m2 or < 85th BMI percentile) Korean adolescents aged 13-16 years and subjected to 16S rRNA gene sequencing. Analysis of bacterial composition according to taxonomic rank (genus, family, and phylum) revealed marked differences in the Bacteroides and Prevotella populations in normal and obese samples (p < 0.005) at the genus and family levels; however, there was no difference in the Firmicutes-to-Bacteroidetes (F/B) ratio between normal and obese adolescents samples at the phylum level (F/B normal = 0.50 ± 0.53; F/B obese = 0.56 ± 0.86; p = 0.384). Statistical analysis revealed a significant association between the compositions of several bacterial taxa and child obesity. Among these, Bacteroides and Prevotella showed the most significant association with BMI (p < 0.0001 and 0.0001, respectively). We also found that the composition of Bacteroides was negatively associated with triglycerides (TG), total cholesterol, and high-sensitive C-reactive protein (hs-crp) (p = 0.0049, 0.0023, and 0.0038, respectively) levels, whereas that of Prevotella was positively associated with TG and hs-crp levels (p = 0.0394 and 0.0150, respectively). We then applied the association rule mining algorithm to generate "rules" to identify the association between the populations of multiple bacterial taxa and obesity; these rules were able to discriminate obese from normal states. Therefore, the present study describes a systemic approach to identify the association between bacterial populations in the gut and childhood obesity.
This study aimed to validate body composition analysis using bioelectrical impedance analysis (BIA) against dual‐energy X‐ray absorptiometry (DXA) in children with obesity and to compare agreement ...between BIA and DXA according to their degree of obesity. Three hundred and sixteen children aged 6‐17 years participated in the Intervention for Childhood and Adolescents Obesity via Activity and Nutrition study. We divided participants by body mass index (BMI) percentile (group 1: mild to moderate obesity; group 2: severe obesity) and compared body composition variables, eg, percentage of body fat (%BF), fat mass (FM), and fat‐free mass (FFM) using BIA and DXA. The %BF and FM of BIA were significantly lower (−1.8% and −0.8 kg, respectively), and the FFM of BIA was significantly higher (1.4 kg) than those of DXA. There were significant negative relationships between the absolute value of differences from BIA and DXA and BMI z‐scores in %BF, FM, and FFM (regression coefficient β: −1.39, 95% confidence interval CI: −1.81 to −0.97; β: −0.34, 95%CI: −0.61 to −0.06; β: −0.73, 95%CI: −1.03 to −0.44, respectively). The gap of body compositions between BIA and DXA decreased as participants became more obese, and the differences of FM in boys with severe obesity and the differences of %BF and FFM in girls with severe obesity were much less than those in children with mild to moderate obesity. In conclusion, the agreement between DXA and BIA was better for children with severe obesity than for children with mild to moderate obesity.
This study aimed to develop a multidisciplinary lifestyle intervention program targeted at children and adolescents with moderate to severe obesity, and assess the additional effects of exercise ...intervention when compared to usual care. Overall, the 103 enrolled participants were ≥85th percentile of age and sex-specific body mass index (BMI). Participants were divided into groups that received 16 weeks of either usual care or exercise intervention. The BMI
-score of the overall completers decreased by about 0.05 after the 16-week intervention (
= 0.02). After the intervention, only the exercise group had a significantly lower BMI
-score than the baseline score by about 0.1 (
= 0.03), but no significant group by time interaction effects were observed. At the 16-week follow-up, significant group by time interaction effects were observed in percentage body fat (%BF) (β = -1.52, 95%CI = -2.58⁻-0.45), lean body mass (LM) (β = 1.20, 95%CI = 0.12⁻2.29), diastolic blood pressure (β = -5.24, 95%CI = -9.66⁻-0.83), high-sensitivity C-reactive protein (β = -1.67, 95%CI = -2.77⁻-1.01), and wall sit test score (β = 50.74, 95%CI = 32.30⁻69.18). We developed a moderate-intensity intervention program that can be sustained in the real-world setting and is practically applicable to both moderate and severe obesity. After interventions, the exercise group had lower %BF and cardiometabolic risk markers, and higher LM and leg muscle strength compared to the usual care group.
Insulin resistance is an important clinical feature of metabolic syndrome, which includes obesity and type 2 diabetes. Increased adipose energy storage in obesity promote insulin resistance and other ...metabolic adverse effects. To identify a new link between adipocyte and insulin resistance, we performed targeted metabolite profiling of differentiated adipocytes and studied the association between adipogenic metabolites and insulin resistance. We found a correlation between 2-aminoadipic acid (2-AAA) and adipogenic differentiation. Also, circulatory 2-AAA was positively associated with obesity-related factors (fat mass, fat percent, waist circumference, BMI, BMI z-score, triglycerides, insulin, and HOMA-IR) at baseline and after 2 years in the children cohort study. Of these factors, increased BMI z-score and HOMA-IR were the primary independent factors associated with higher 2-AAA levels, and the baseline 2-AAA level was an indicator of the BMI z-score after 2 years. To validate the relationship between 2-AAA and obesity-related factors, we analyzed changes in 2-AAA levels following obesity intervention programs in two independent studies. In both studies, changes in 2-AAA levels during the intervention period were positively correlated with changes in the BMI z-score and HOMA-IR after adjusting for confounders. Moreover, the 2-AAA levels were increased in cell and mouse models of obesity-related insulin resistance. Excess 2-AAA levels led to impaired insulin signaling in insulin-sensitive cells (liver, skeletal muscle and adipose cells) and caused abnormal gluconeogenesis. Our results demonstrate that 2-AAA is associated with adipogenesis and insulin resistance. In this regard, 2-AAA could be a potential biomarker of obesity and obesity-related metabolic disorders.
Abstract
Alcohol consumption is associated with a high increased lipid profile and this association may depend on genetic risk factors. In this study, we aimed to assess the effects of genetic ...variation associated with alcohol consumption on lipid profiles using data from two Korean population studies. We performed a genotype association study using the HEXA (
n
= 51,349) and KNHANES (
n
= 9158) data. Genotype analyses of the two sets of Korean population data showed associations of increased total cholesterol and high-density lipoprotein (HDL)-cholesterol with
CETP
rs708272. The HEXA and KNHANES populations revealed differences in HDL cholesterol according to the presence of
CETP
rs708272, independent of
ALDH2
rs671 and alcohol consumption. In contrast, total cholesterol levels were associated with alcohol consumption and
ALDH2
rs671 in men with
CETP
rs708272 (CT and TT genotypes). Furthermore, in drinkers with
ALDH2
rs671 (GA and AA genotypes), higher total cholesterol was associated with the
CETP
rs708272 TT minor homozygous genotype based on both HEXA and KNHANES data. Our findings demonstrated that alcohol consumption and genetic variation in either
CETP
or
ALDH2
may be associated with cholesterol levels. We hope these findings will provide a better understanding of the relationship between alcohol consumption and cholesterol according to each individual’s genetic background.
Glutamate is a major neurotransmitter, although it causes cytotoxicity and inflammation in nonneuronal organs. This study aimed to investigate the metabolic disorders in which glutamate, associated ...with type 2 diabetes onset, is induced in the liver.
An analysis of Korean community-based Ansan-Ansung cohort study data as well as functional research using in vitro and mouse models were performed.
Groups with high plasma glutamate levels (T2, T3) had a significantly increased risk of diabetes incidence after 8 years, compared to the group with relatively low glutamate levels (T1). Analysis of the effect of glutamate on diabetes onset in vitro showed that glutamate induces insulin resistance by increasing glucose-related protein 78 (GRP78) and phosphoenolpyruvate carboxykinase (PEPCK) expression in SK-Hep-1 human liver cells. In addition, three different genes, FRMB4B, PLG, and PARD3, were significantly associated with glutamate and were identified via genome-wide association studies. Among glutamate-related genes, plasminogen (PLG) levels were most significantly increased in several environments in which insulin resistance was induced, and was also upregulated by glutamate. Glutamate-induced increase in PLG in liver cells was caused by metabotropic glutamate receptor 5 activation, and PLG levels were also upregulated after extracellular secretion. Moreover, glutamate increased the expression of plasminogen activator inhibitor-1 (PAI-1). Thus, extracellular secreted PLG cannot be converted to plasmin (fibrinolytic enzyme) by increased PAI-1.
Increased glutamate is closely associated with the development of diabetes, and it may cause metabolic disorders by inhibiting the fibrinolytic system, which plays an important role in determining blood clots, a hallmark of diabetes.
The early identification of predictors related to cardiovascular disease risk factor clustering (CVD-RFC) can help prevent chronic disease. We aimed to identify the risk factors for CVD-RFC in ...adolescents.
A prospective longitudinal cohort study design was used to obtain data included in these analyses from school-aged children who participated in the Korean Child-Adolescent Study 2008-2014. A total of 1309 children aged 6-15 years were enrolled. We compared the participants based on the presence or absence of CVD-RFC and examined the cumulative incidence of CVD-RFC.
Of the total 1309 children, 410 (31.32%) had CVD-RFC in adolescence. A higher average household income ≥3 million Korean Republic won (KRW)/month (3-5 million KRW/month: HR 0.75 (95% CI 0.58 to 0.97); ≥5 million KRW/month: HR 0.58 (95% CI 0.44 to 0.77)) was associated with a lower CVD-RFC incidence, while the presence of parental CVD history (HR 1.28 (95% CI 1.04 to 1.57)), overweight or obesity (HR 3.83 (95% CI 3.05 to 4.80)) and shorter sleep duration of 8-9 hour/day (HR 1.80 (95% CI 1.05 to 3.07)) and <8 hour/day (HR 1.93 (95% CI 1.11 to 3.34)) had higher CVD-RFC incidences.
Obesity in childhood, short sleep duration and parental factors such as low socioeconomic status and parental history of CVD are significant risk factors for the development of CVD-RFC in adolescents. Efforts to create awareness regarding sufficient sleep duration in children via intervention programmes targeting cardiometabolic health in children and special attention to lifestyle modifications and socioeconomic components of the family should be considered.
Alzheimer's disease (AD) is the most common cause of dementia in individuals over 65years old. However, to date, no useful early diagnostic markers for AD have been discovered. We examined the ...utility of plasminogen activator inhibitor-1 (PAI-1) as a potential biomarker for AD in subjects with mild cognitive impairment (MCI) or AD, as well as in nondemented healthy controls. Plasma PAI-1 levels were measured by enzyme-linked immunosorbent assays (ELISAs) in samples collected from 76 patients with MCI, 74 patients with AD, and 76 healthy controls. Our results show that plasma PAI-1 levels gradually increased as dementia progressed. The mean levels of plasma PAI-1 in patients with MCI and AD patients were significantly higher than those of in healthy controls. Consistently, neuropsychological examination (e.g., MMSE, CDR) also demonstrated significant correlations between the plasma PAI-1 levels and cognitive function. In conclusion, the level of plasma PAI-1 is a potential biomarker for the early detection and diagnosis of AD.
•We examined the utility of plasma PAI-1 as an early diagnostic marker for AD.•The plasma levels of PAI-1 increased in MCI and AD compared to healthy controls.•Increment of PAI-1 represented the correlation with decline of cognitive function.•We suggest the role of PAI-1 protein as a potential early diagnostic marker in AD.
Moderate alcohol consumption is generally associated with reduced risk of type 2 diabetes. However, this beneficial effects of alcohol intake remains controversial due to inconsistent results across ...studies. The analysis was performed using data from the Ansung-Ansan cohort study. We categorized the participants into four groups-based on the baseline (one-point measure; non-drinking, <5 g/day, ≥5, <30 g/day, and ≥30 g/day) and follow-up (consumption pattern; never-drinking, light, moderate, and heavy drinking) measurement. At baseline, ≥30 g/day alcohol consumption increased the risk of incident diabetes (HR: 1.42; 95% CI, 1.10-1.85), but ≥5, <30 g/day alcohol consumption had no effects on the incident diabetes. Meanwhile, when using the alcohol consumption pattern, a heavy-drinking pattern increased the risk of incident diabetes (HR = 1.32, 1.01-1.73), but the light and moderate consumption pattern was associated with a reduced risk of type 2 diabetes (HR: 0.66; 0.50-0.87 and HR: 0.74; 0.57-0.95, respectively). At the end point of follow-up, the insulinogenic index (IGI), but not the insulin sensitivity index (ISI), differed among the groups. Alcohol consumption pattern had a J-shaped association with the incident type 2 diabetes in Korean men. The IGI showed an inverted J-shaped association according to alcohol drinking pattern, but the ISI was not a J-shape.
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