Ultra-processed Food Intake and Risk of Type 2 Diabetes in Korean Adults.

BACKGROUND: Several studies from the United States and European countries reported a positive association between ultra-processed food intake and diabetes risk. However, little is known about the association in Asian populations. It is also unknown about the individual ultra-processed food items that are most unfavorably associated with diabetes risk. OBJECTIVE: We examined the associations of ultra-processed food intake (combined, as well as individual ultra-processed food items) with the risk of type 2 diabetes. METHODS: This prospective analysis included 7438 participants aged 40-69 y from the Korean Genome and Epidemiology Study Ansan-Ansung cohort. Dietary intake was assessed at baseline using a 103-item semiquantitative food-frequency questionnaire. Ultra-processed foods were classified using the Nova definition. Incident type 2 diabetes cases were identified via follow-up interviews and health examination. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: During the follow-up (2001-2019; median: 15 y), a total of 1187 type 2 diabetes cases were identified. Compared with the lowest quartile of ultra-processed food intake, the highest quartile was positively associated with diabetes risk [HR (95% CI) = 1.34 (1.13, 1.59), P-trend = 0.002]. The association did not change after additional adjustment for diet quality or BMI. Among individual ultra-processed food items, a higher consumption of ham/sausage [per 1% increase in the weight ratio: HR (95% CI) = 1.40 (1.05, 1.86)], instant noodles [1.07 (1.02, 1.11)], ice cream [1.08 (1.03, 1.13)], and carbonated beverages [1.02 (1.00, 1.04)] were associated with an increased risk of type 2 diabetes, whereas a higher intake of candy/chocolate was associated with a decreased risk [0.78 (0.62, 0.99)]. CONCLUSIONS: Our data suggest that the high intake of ultra-processed foods, particularly ham/sausage, instant noodles, ice cream, and carbonated beverages, is associated with an increased risk of type 2 diabetes in Korean adults.

Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model. Immortalized human epidermal keratinocytes were transduced with a recombinant adenovirus expressing microRNA specific for WWOX to downregulate its expression. Inflammatory responses were detected using Western blotting, real-time quantitative reverse transcription polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay. In human epidermal keratinocytes, WWOX knockdown reduced nuclear factor-kappa B signaling and levels of proinflammatory cytokines induced by polyinosinic: polycytidylic acid [(poly(I:C)] in vitro. Furthermore, calcium chelator and protein kinase C (PKC) inhibitors significantly reduced poly(I:C)-induced inflammatory reactions. WWOX plays a role in the inflammatory reaction of epidermal keratinocytes by regulating calcium and PKC signaling. Targeting WWOX could be a novel therapeutic approach for psoriasis in the future.

Biglycan reduces body weight by regulating food intake in mice and improves glucose metabolism through AMPK/AKT dual pathways in skeletal muscle.

While biglycan (BGN) is suggested to direct diverse signaling cascades, the effects of soluble BGN as a ligand on metabolic traits have not been studied. Herein, we tested the effects of BGN on obesity in high-fat diet (HFD)-induced obese animals and glucose metabolism, with the underlying mechanism responsible for observed effects in vitro. Our results showed that BGN administration (1 mg/kg body weight, intraperitoneally) significantly prevented HFD-induced obesity, and this was mainly attributed to reduced food intake. Also, intracerebroventricular injection of BGN reduced food intake and body weight. The underlying mechanism includes modulation of neuropeptides gene expression involved in appetite in the hypothalamus in vitro and in vivo. In addition, BGN regulates glucose metabolism as shown by improved glucose tolerance in mice as well as AMPK/AKT dual pathway-driven enhanced glucose uptake and GLUT4 translocation in L6 myoblast cells. In conclusion, our results suggest BGN as a potential therapeutic target to treat risk factors for metabolic diseases.

Recyclable Periodic Nanostructure Formed by Sublimable Liquid Crystals for Robust Cell Alignment.

We demonstrate a facile method to fabricate a recyclable cell-alignment scaffold using nanogrooves based on sublimable liquid crystal (LC) material. Randomly and uniaxially arranged smectic LC structures are obtained, followed by sublimation and recondensation processes, which directly produce periodic nanogrooves with dimensions of a couple of hundreds of nanometers. After treatment with osmium tetroxide (OsO4), the nanogroove can serve as a scaffold to efficiently induce directed cell growth without causing cytotoxicity, and it can be used repeatedly. Together, various cell types are applied to the nanogroove, proving the scaffold's broad applicability. Depending on the nanotopography of the LC structures, cells exhibit different morphologies and gene expression patterns, compared to cells on standard glass substrates, according to microscopic observation and qPCR. Furthermore, cell sheets can be formed, which consist of oriented cells that can be repeatedly formed and transferred to other substrates, while maintaining its organization. We believe that our cell-aligning scaffold may pave the way for the soft material field to bioengineering, which can involve fundamentals in cell behavior and function, as well as applications for regenerative medicine.

Effect of chitinase-3-like protein 1 on glucose metabolism: In vitro skeletal muscle and human genetic association study.

We investigated the effect of chitinase-3-like protein 1 (CHI3L1) on glucose metabolism and its underlying mechanisms in skeletal muscle cells, and evaluated whether the observed effects are relevant in humans. CHI3L1 was associated with increased glucose uptake in skeletal muscles in an AMP-activated protein kinase (AMPK)-dependent manner, and with increased intracellular calcium levels via PAR2. The improvement in glucose metabolism observed in an intraperitoneal glucose tolerance test on male C57BL/6J mice supported this association. Inhibition of the CaMKK was associated with suppression of CHI3L1-mediated glucose uptake. Additionally, CHI3L1 was found to influence glucose uptake through the PI3K/AKT pathway. Results suggested that CHI3L1 stimulated the phosphorylation of AS160 and p38 MAPK downstream of AMPK and AKT, and the resultant GLUT4 translocation. In primary myoblast cells, stimulation of AMPK and AKT was observed in response to CHI3L1, underscoring the biological relevance of CHI3L1. CHI3L1 levels were elevated in cells under conditions that mimic exercise in vitro and in exercised mice in vivo, indicating that CHI3L1 is secreted during muscle contraction. Finally, similar associations between CHI3L1 and metabolic parameters were observed in humans alongside genotype associations between CHI3L1 and diabetes at the population level. CHI3L1 may be a potential therapeutic target for the treatment of diabetes.

ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways.

ATPase inhibitory factor 1 (IF1) is an ATP synthase-interacting protein that suppresses the hydrolysis activity of ATP synthase. In this study, we observed that the expression of IF1 was up-regulated in response to electrical pulse stimulation of skeletal muscle cells and in exercized mice and healthy men. IF1 stimulates glucose uptake via AMPK in skeletal muscle cells and primary cultured myoblasts. Reactive oxygen species and Rac family small GTPase 1 (Rac1) function in the upstream and downstream of AMPK, respectively, in IF1-mediated glucose uptake. In diabetic animal models, the administration of recombinant IF1 improved glucose tolerance and down-regulated blood glucose level. In addition, IF1 inhibits ATP hydrolysis by ß-F1-ATPase in plasma membrane, thereby increasing extracellular ATP and activating the protein kinase B (Akt) pathway, ultimately leading to glucose uptake. Thus, we suggest that IF1 is a novel myokine and propose a mechanism by which AMPK and Akt contribute independently to IF1-mediated improvement of glucose tolerance impairment. These results demonstrate the importance of IF1 as a potential antidiabetic agent.-Lee, H. J., Moon, J., Chung, I., Chung, J. H., Park, C., Lee, J. O., Han, J. A., Kang, M. J., Yoo, E. H., Kwak, S.-Y., Jo, G., Park, W., Park, J., Kim, K. M., Lim, S., Ngoei, K. R. W., Ling, N. X. Y., Oakhill, J. S., Galic, S., Murray-Segal, L., Kemp, B. E., Mantzoros, C. S., Krauss, R. M., Shin, M.-J., Kim, H. S. ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways.

Sleep duration and mortality in Korean adults: a population-based prospective cohort study.

BACKGROUND: Increasing evidence suggests that sleep duration is associated with risks of various diseases including type 2 diabetes, cardiovascular disease (CVD), and certain types of cancer. However, the relationship with mortality is not clear, particularly in non-European populations. In this study, we investigated the association between sleep duration and mortality in a population-based prospective cohort of Korean adults. METHODS: This analysis included 34,264 participants (14,704 men and 19,560 women) of the Korea National Health and Nutrition Examination Survey (KNHANES) 2007-2013 who agreed to mortality follow-up through December 31, 2016. Sleep duration was self-reported at baseline and was categorized into four groups: ≤4, 5-6, 7-8, and ≥ 9 h/day. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations with mortality (all-cause as well as CVD- and cancer-specific), adjusting for potential confounders. RESULTS: During up to 9.5 years of follow-up, we identified a total of 1028 deaths. We observed the lowest mortality at 5-6 h/day sleep. Compared with 7-8 h/day of sleep, short (≤4 h/day) and long (≥9 h/day) sleep were associated with a 1.05-fold (95% CI = 0.79-1.39) and 1.47-fold (95% CI = 1.15-1.87) higher all-cause mortality, respectively. After additional adjustment for self-rated health, the positive association with short sleep disappeared (HR = 0.99, 95% CI = 0.75-1.32) and the association with long sleep was slightly attenuated (HR = 1.38, 95% CI = 1.08-1.76). Long sleep was also nonsignificantly positively associated with both cancer-mortality (HR = 1.30, 95% CI = 0.86-1.98) and CVD-mortality (HR = 1.27, 95% CI = 0.73-2.21). There was no statistically significant evidence for nonlinearity in the relationships between sleep duration and mortality (all-cause as well as CVD- and cancer-specific). Effect modification by age, sex, education, and occupation were not statistically significant. CONCLUSIONS: Our findings suggest that long sleep duration is associated with an increased all-cause mortality in Korean adults.

Medium-Chain Acylcarnitines Are Associated With Cardioembolic Stroke and Stroke Recurrence.

Objective- Stroke is a heterogeneous disease with diverse causes, which affect the risk of recurrence. This study aimed to identify novel biomarkers that are clinically relevant to the diagnosis of cardioembolic stroke (CE) and the prediction of stroke recurrence using metabolomics. Approach and Results- We obtained blood samples and clinical data from a consecutively registered, hospital-based acute stroke registry and from healthy controls. Mass-spectrometry-based profiling was performed, and several metabolomic signatures were selected for the discrimination of CE and stroke recurrence, coupled with multivariate statistical analysis. Finally, 190 acute ischemic stroke participants (43 CE patients and 147 non-CE patients) and 30 control participants were included. We obtained 29 metabolomics signatures, and of these, 2 medium-chain acylcarnitines (decanoylcarnitine and octanoylcarnitine) were selected as independent discriminants for CE (odds ratio, 2.839; 95% CI, 1.241-6.493 for decanoylcarnitine; odds ratio, 2.839; 95% CI, 1.241-6.493 for octanoylcarnitine). Elevated medium-chain acylcarnitines were also associated with a higher risk of stroke recurrence (hazard ratio, 3.767; 95% CI, 1.276-11.117 for decanoylcarnitine; hazard ratio, 5.519; 95% CI, 1.22-18.781 for octanoylcarnitine). The levels of decanoylcarnitine and octanoylcarnitine were correlated as known surrogate markers of CE. The levels of decanoylcarnitine and octanoylcarnitine were significantly higher in stroke patients with a high-risk potential of cardioembolism than in those with low or intermediate risk. Conclusions- Metabolomics provided an improved understanding of CE pathogenesis and stroke recurrence. We have identified decanoylcarnitine and octanoylcarnitine as novel biomarkers for CE and stroke recurrence.

Association between sugar-sweetened beverage consumption and incident hypertension in Korean adults: a prospective study.

PURPOSE: Epidemiological information on the association between sugar-sweetened beverage (SSB) consumption and the risk for hypertension (HTN) in Koreans is very limited. We tested the hypothesis that increased SSB consumption is related to a higher risk of HTN among middle-aged Korean adults in a Korean community-based cohort. METHODS: From participants of the cohort from 2001 to 2010, we selected 5775 subjects without HTN, diabetes, cardiovascular disease, and cancer and who had no information on dietary assessment at baseline. To assess the relationship between SSB consumption and HTN, we estimated hazard ratios (HRs) and 95% confidence intervals using Cox regression analysis. In addition, stratified analysis by body mass index (BMI) was conducted. RESULTS: During the follow-up, we identified 1175 cases of incident HTN. The adjusted HR of HTN for the highest quartile of SSB consumption was 1.21 compared to the lowest quartile. Furthermore, higher consumption of SSB was significantly associated with increased incidence of HTN in subjects with BMI ≥ 25 kg/m2, whereas there was no significant association among subjects with BMI < 25 kg/m2. CONCLUSIONS: The results of this study suggest that SSB consumption was associated with an increased risk of HTN, particularly among obese participants.

Voglibose-mediated alterations in neurometabolomic profiles in the hypothalamus of high-fat diet-fed mice.

The alpha-glucosidase inhibitor voglibose (VO) was recently reported to have a protective effect against weight gain as well as affect various metabolic changes related to food intake and gut-brain signaling. We hypothesized that VO prevents weight gain by altering neurometabolome profiles in the hypothalamus to reduce food intake. To test this hypothesis, we assessed metabolite profiles in the hypothalamus of standard diet- or high-fat (HF) diet-fed mice in the absence or presence of VO. In total, 29 male C57BL/6 mice were divided into 3 groups: (1) lean control, (2) HF, and (3) HF + VO. Vehicle or VO was administered for 12 weeks. The results showed that there were alterations in levels of metabolites across several metabolic pathways in the hypothalamus. VO treatment increased levels of many amino acids including arginine, glutamine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine in the hypothalamus. In addition, levels of 2-hydroxy-2-methyl-butyric acid in the hypothalamus were significantly increased after VO administration in HF diet-fed mice. Among lipid metabolites, levels of fatty acids were higher in the hypothalamus of VO-treated mice than in that of HF diet-fed mice. In terms of the energy status, the ATP/ADP ratio was higher in the hypothalamus of VO-treated mice (P < 0.001), thereby indicating an energy surplus. In conclusion, VO supplementation altered metabolite profiles in the hypothalamus to enhance catabolism, which is possibly responsible for the hypophagic effect of VO in HF diet-fed mice.

Serum gamma-glutamyl transferase and risk of type 2 diabetes in the general Korean population: a Mendelian randomization study.

Elevated gamma-glutamyl transferase (GGT) levels are associated with higher risk of type 2 diabetes in observational studies, but the underlying causal relationship is still unclear. Here, we tested a hypothesis that GGT levels have a causal effect on type 2 diabetes risk using Mendelian randomization. Data were collected from 7640 participants in a South Korean population. In a single instrumental variable (IV) analysis using two stage least squares regression with the rs4820599 in the GGT1 gene region as an instrument, one unit of GGT levels (IU/L) was associated with 11% higher risk of type 2 diabetes (odds ratio (OR) = 1.11, 95% confidence interval (CI): 1.04 to 1.19). In a multiple IV analysis using seven genetic variants that have previously been demonstrated to be associated with GGT at a genome-wide level of significance, the corresponding estimate suggested a 2.6% increase in risk (OR = 1.026, 95% CI: 1.001 to 1.052). In a two-sample Mendelian randomization analysis using genetic associations with type 2 diabetes taken from a trans-ethnic GWAS study of 110 452 independent samples, the single IV analysis confirmed an association between the rs4820599 and type 2 diabetes risk (P-value = 0.04); however, the estimate from the multiple IV analysis was compatible with the null (OR = 1.007, 95% CI: 0.993 to 1.022) with considerable heterogeneity between the causal effects estimated using different genetic variants. Overall, there is weak genetic evidence that GGT levels may have a causal role in the development of type 2 diabetes.

Directed Self-Assembly of Topological Defects of Liquid Crystals.

One of the alluring aspects of liquid crystals (LCs) is their readily controllable self-assembly behavior, leading to comprehension of complex topological structures and practical patterning applications. Here, we report on manipulating various kinds of topological defects by adopting an imprinted polymer-based soft microchannel that simultaneously imposes adjustable surface anchoring, confinement, and uniaxial alignment. Distinctive molecular orientation could be achieved by varying the surface anchoring conditions at the sidewall polymer and the rubbing directions on the bottom layer. On this pioneering platform, a common LC material, 8CB (4'-n-octyl-4-cyano-biphenyl), was placed where various topological defect domains were generated in a periodic arrangement. The experimental results showed that our platform can change the packing behavior and even the shape of topological defects by varying the rubbing condition. We believe that this facile tool to modulate surface boundary conditions combined with topographic confinement can open a way to use LC materials in potential optical and patterning applications.

Polymer functionalized nanoparticles in liquid crystals: combining PDLCs with LC nanocomposites.

Liquid crystal (LC)-polymer blends are important stimuli responsive materials already employed in a wide range of applications whereas nanoparticle (NP)-LC blends are an emerging class of nanocomposites. Polymer ligands offer the advantages of synthetic simplicity along with chemical and molecular weight tunability. Here we compare the phase behavior of 5CB blended with poly(ethylene oxide) (PEO) and with gold NPs functionalized with thiolated PEO (AuNP-PEO) as a function of PEO concentration by DSC, POM and 13C NMR spectroscopy. Both PEO and the AuNP-PEO form uniform dispersions in isotropic 5CB and phase separate below the I-N phase transition temperature. Above the PEO crystallization temperature, the PEO/5CB blends show the expected biphasic state of PEO rich-isotropic liquid co-existing with PEO-poor nematic droplets. At PEO concentrations above 10 wt%, nematic 5CB nucleates with PEO crystallization. Both PEO and AuNP-PEO induce homeotropic alignment of the 5CB matrix immediately below TNI. The AuNP-PEO/5CB blends form thermally reversible cellular networks similar to AuNPs functionalized with low molecular weight mesogenic ligands. A thermodynamic model to account for the observed phase behavior is presented.

Association among genetic variants in the vitamin D pathway and circulating 25-hydroxyvitamin D levels in Korean adults: results from the Korea National Health and Nutrition Examination Survey 2011-2012.

Vitamin D deficiency affects >60% of the Korean population. Recent reports in Caucasian, African American, and Chinese populations indicate an association between vitamin D status and related single nucleotide polymorphisms (SNPs), but specific associations differ among study populations. We investigated the relationship between five SNPs involved in the vitamin D metabolic pathway (DHCR7 rs12785878, GC rs2282679, CYP2R1 rs12794714, CYP2R1 rs10741657, and CYP24A1 rs6013897) and serum 25-hydroxyvitamin D [25(OH)D] status in Koreans using the Korea National Health and Nutrition Examination Survey, a nationwide database. Whether the association was modified by demographic and lifestyle factors, including sex, body mass index (BMI), smoking status, drinking status, physical activity, and sun exposure, were also investigated. The results showed the serum level of 25(OH)D was associated with rs12785878, rs2282679, and rs12794714 genotypes, but not with rs10741657 or rs6013897. The genetic risk score (GRS) calculated by summing the number of alleles of these 5 SNPs was associated with low circulating levels of 25(OH)D. However, the negative association between 25(OH)D and GRS was modified by obesity and sun exposure. Specifically, negative associations between 25(OH)D and GRS were present in adults with lower BMI (<25 kg/m2) and longer sun exposure time (≥2 h/day). In conclusion, common variants of vitamin D-related SNPs are associated with vitamin D status in Koreans, and this genetic effect was masked when BMI ≥25 kg/m2 or sun exposure <2 h/day. Additionally, seasonal variation must be considered in future studies among Koreans.

Selected Food Consumption Mediates the Association between Education Level and Metabolic Syndrome in Korean Adults.

BACKGROUND/AIMS: Low socioeconomic status (SES) is linked to higher incidence/mortality of cardiovascular disease, but emerging evidence inconsistently reported that education level, a proxy for SES, is related to cardiovascular risk and metabolic syndrome (MetS) in Koreans. Furthermore, limited information is available on whether dietary components would mediate the relationship between education level and cardiovascular risk. We hypothesized that selected food consumption mediates the association between education level and MetS prevalence. METHODS: Data from the Korea National Health and Nutritional Examination Survey (2008-2011) were included in cross-sectional analyses (n = 11,029, 30-64 years). The possible mediating effect of selected food groups (fruits, raw vegetables, red meat, milk, and soft drinks) on the association between education level and MetS was tested using a multiple mediation model. RESULTS: Education level was negatively associated with MetS prevalence. The association between lower education level and higher MetS prevalence was partially mediated by selected food consumption (lower intakes of fruit, red meat and milk; higher intakes of vegetable and soft drink) after adjusted for covariates. Gender also modified the association between education level and MetS prevalence that was more prominent in women than in men. CONCLUSIONS: Selected food consumption substantially contributes to the association between education level and MetS in Korean adults, especially among women.

Risk of secondary lymphedema in breast cancer survivors is related to serum phospholipid fatty acid desaturation.

PURPOSE: Secondary lymphedema is a common irreversible side effect of breast cancer surgery. We investigated if risk of secondary lymphedema in breast cancer survivors was related to changes in serum phospholipid fatty acid composition. METHODS: Study subjects were voluntarily recruited into the following three groups: breast cancer survivors who had sentinel lymph node biopsy without lymphedema (SLNB), those who had auxillary lymph node dissection without lymphedema (ALND), and those who had ALND with lymphedema (ALND + LE). Body mass index (BMI), serum lipid profiles, bioimpedance data with single-frequency bioimpedance analysis (SFBIA), and serum phospholipid compositions were analyzed and compared among the groups. RESULTS: BMI, serum total cholesterol (total-C), and low-density lipoprotein cholesterol (LDL-C) and SFBIA ratios increased only in the ALND + LE. High polyunsaturated fatty acids (PUFAs) and high C20:4 to C18:2 n-6 PUFAs (arachidonic acid [AA]/linoleic acid [LA]) was detected in the ALND and ALND + LE groups compared to SLNB. The ALND + LE group showed increased activity indices for delta 6 desaturase (D6D) and D5D and increased ratio of AA to eicosapentaenoic acid (AA/EPA) compared to the ALND and SLNB groups. Correlation and regression analysis indicated that D6D, D5D, and AA/EPA were associated with SFBIA ratios. CONCLUSION: We demonstrated that breast cancer survivors with lymphedema had elevated total PUFAs, fatty acid desaturase activity indices, and AA/EPA in serum phospholipids. Our findings suggested that desaturation extent of fatty acid composition might be related to the risk of secondary lymphedema in breast cancer survivors.

Association of dietary intakes of total and subtypes of fat substituted for carbohydrate with metabolic syndrome in Koreans.

Amount of fat consumption has gradually increased among Koreans, which is relatively lower than western countries. In the current study, we examined the association between dietary fat and metabolic syndrome (MetS) prevalence among Korean adults. 3,212 participants who are aged 30-74 years from the Korea National Health and Nutritional Examination Survey (KNHANES) VI (2013) were included for cross-sectional analyses. Dietary intake data was assessed using 24-hour recall method, and MetS was defined using guideline of the National Cholesterol Education Program Adult Treatment panel III (NCEP-ATP III). Multivariate logistic regression analysis was used to estimate MetS odds ratios, using nutrient density model, according to 5% percent unit of dietary fat intake. The prevalence of MetS was significantly associated with dietary intake of total fat and saturated fatty acid (SFA) after adjustment (odds ratio [OR] 0.984 95% confidence interval [CI] 0.972-0.996; OR 0.946 95% CI 0.915-0.979). When dietary intake of total fat and SFA were substituted for carbohydrate (CHO), ORs for MetS were 0.985 (95% CI 0.972-0.998) and 0.948 (95% CI 0.907-0.990), respectively, after adjusting for potential covariates. In summary, MetS was significantly associated with dietary intakes of total fat and SFA, and when substituting dietary fat for carbohydrate among Koreans.

Beneficial effects of voglibose administration on body weight and lipid metabolism via gastrointestinal bile acid modification.

This study was designed with the goal of examining the effects of voglibose administration on body weight and lipid metabolism and underlying mechanism high fat diet-induced obese mice. Male C57BL/6 mice were randomly assigned to one of four groups: a control diet (CTL), high-fat diet (HF), high-fat diet supplemented with voglibose (VO), and high fat diet pair-fed group (PF). After 12 weeks, the following characteristics were investigated: serum lipid and glucose levels, serum polar metabolite profiles, and expression levels of genes involved in lipid and bile acid metabolism. In addition, pyrosequencing was used to analyze the composition of gut microbiota found in feces. Total body weight gain was significantly lower in the VO group than in the CTL, HF, and PF groups. The VO group exhibited improved metabolic profiles including those of blood glucose, triglyceride, and total cholesterol levels. The 12-week voglibose administration decreased the ratio of Firmicutes to Bacteroidetes found in feces. Circulating levels of taurocholic and cholic acid were significantly higher in the VO group than in the HF and CTL groups. Deoxycholic acid levels tended to be higher in the VO group than in the HF group. Voglibose administration downregulated expression levels of CYP8B1 and HNF4α genes and upregulated those of PGC1α, whereas FXRα was not affected. Voglibose administration elicits changes in the composition of the intestinal microbiota and circulating metabolites, which ultimately has systemic effects on body weight and lipid metabolism in mice.

Arginase inhibition ameliorates adipose tissue inflammation in mice with diet-induced obesity.

This study examined whether oral administration of an arginase inhibitor regulates adipose tissue macrophage infiltration and inflammation in mice with high fat diet (HFD)-induced obesity. Male C57BL/6 mice (n = 30) were randomly assigned to control (CTL, n = 10), HFD only (n = 10), and HFD with arginase inhibitor N(ω)-hydroxy-nor-l-arginine (HFD with nor-NOHA, n = 10) groups. Plasma and mRNA levels of cytokines in epididymal adipose tissues (EAT), macrophage infiltration into EAT, and macrophage phenotype polarization were measured in the animals after 12 weeks. Additionally, the effects of nor-NOHA on adipose tissue macrophage infiltration and mRNA expression of cytokines were measured in co-cultured 3T3-L1 adipocytes and RAW 264.7 macrophages. Macrophage infiltration into the adipocytes was significantly suppressed by nor-NOHA treatment in adipocyte/macrophage co-culture system and mice with HFD-induced obesity. Pro-inflammatory cytokines, including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), were significantly downregulated, and the anti-inflammatory cytokine IL-10 was significantly upregulated in nor-NOHA-treated co-cultured cells. In the mice with HFD-induced obesity, plasma and mRNA levels of MCP-1 significantly reduced after supplementation with nor-NOHA. In addition, oral supplement of nor-NOHA modified M1/M2 phenotype ratio in the EAT. Oral supplementation of an arginase inhibitor, nor-NOHA, altered M1/M2 macrophage phenotype and macrophage infiltration into HFD-induced obese adipose tissue, thereby improved adipose tissue inflammatory response. These results may indicate that arginase inhibition ameliorates obesity-induced adipose tissue inflammation.

Association between age at menarche and diabetes in Korean post-menopausal women: results from the Korea National Health and Nutrition Examination Survey (2007-2009).

Early menarche is known to be associated with diabetes, however this association remains controversial. Our study aimed to investigate the possible association between age at menarche and diabetes prevalence in post-menopausal Korean women. This study included 3,254 post-menopausal Korean women aged 50-85 years from the Korea National Health and Nutrition Examination Survey IV (KNHANES 2007-2009). Logistic regression analyses were used to estimate odds ratios (ORs) for diabetes prevalence. Levels of biochemical markers were compared according to groups by age at menarche. Women in the earlier menarche age group (10-12 years) showed higher levels of fasting blood glucose (FBG) and scores of homeostatic model assessment in the insulin resistance (HOMA-IR) index than other groups (p <0.05). After adjusting for potential confounding factors, early age at menarche was significantly associated with a higher prevalence of diabetes (OR 1.86, 95% confidence intervals [CI] 1.07-3.23). The observed association remained significant despite additional adjustment for body mass index and waist circumference (OR 1.82, 95% CI 1.03-3.23) and despite further adjustments for FBG levels and HOMA-IR index (OR 2.25, 95% CI 1.11-4.55). Our findings strengthen the hypothesis that younger age at menarche is associated with increased diabetes prevalence in the Korean population.