The importance of BDNF and RAGE in diabetes-induced dementia.

Diabetes-induced dementia is an emerging neurodisorder all over the world. The prevalence rates of dementia and diabetes have been gradually increasing worldwide. Diabetes has been known to lead to oxidative stress, inflammation aggravation, and hyperglycemia conditions in the brain. Various diabetic implications cause the lower secretion of brain-derived neurotrophic factor (BDNF) and the increase of receptor for advanced glycation end products (RAGE), ultimately leading to both cerebrovascular dysfunction and cognitive decline. Here, we summarized the significant evidences highlighting the specific mechanisms between BDNF and RAGE and cerebrovascular dysfunction and memory function and how these relate to diabetes-induced dementia. Especially, we review that the association between BDFN and RAGE in neuroinflammation, the reduction of long-term potentiation, and the vascular implications in brain.

Effect of resveratrol on adipokines and myokines involved in fat browning: Perspectives in healthy weight against obesity.

Obesity is a globally widespread metabolic disorder, characterized by immoderate fat accumulation in the body. There are different types of body fats such as white adipose tissue (WAT), which stores surplus energy in the body, and brown adipose tissue (BAT) which utilize energy to produce heat during metabolism. BAT acts many beneficial functions in metabolic disorders including type 2 diabetes and obesity. Recent studies have investigated methods for promoting the fat browning process of WAT in obesity because of various reasons such as the improvement of insulin resistance, and weight loss. Among natural polyphenolic compounds, resveratrol has been highlighted due to its anti-oxidant and anti-obesity as well as anti-inflammation and anti-cancer properties. Recent studies have paid a lot of attention to that resveratrol may act as a fat browning activator, involved in the secretion of many myokines and adipokines. Here, we reviewed the role of resveratrol in fat browning and also the association between resveratrol and adipokines/myokines in the fat browning process. Our review may provide novel insight into the role of resveratrol in fat browning, leading to the maintenance of a healthy weight against obesity.

Anti-Neuroinflammatory Property of Phlorotannins from Ecklonia cava on Aß25-35-Induced Damage in PC12 Cells.

Alzheimer disease (AD) is a neurodegenerative disorder characterized by excessive accumulation of amyloid-beta peptide (Aß) and progressive loss of neurons. Therefore, the inhibition of Aß-induced neurotoxicity is a potential therapeutic approach for the treatment of AD. Ecklonia cava is an edible brown seaweed, which has been recognized as a rich source of bioactive derivatives, mainly phlorotannins. In this study, phlorotannins including eckol, dieckol, 8,8'-bieckol were used as potential neuroprotective candidates for their anti-apoptotic and anti-inflammatory effects against Aß25-35-induced damage in PC12 cells. Among the tested compounds, dieckol showed the highest effect in both suppressing intracellular oxidative stress and mitochondrial dysfunction and activation of caspase family. Three phlorotannins were found to inhibit TNF-α, IL-1ß and PGE2 production at the protein levels. These result showed that the anti-inflammatory properties of our compounds are related to the down-regulation of proinflammatory enzymes, iNOS and COX-2, through the negative regulation of the NF-κB pathway in Aß25-35-stimulated PC12 cells. Especially, dieckol showed the strong anti-inflammatory effects via suppression of p38, ERK and JNK. However, 8,8'-bieckol markedly decreased the phosphorylation of p38 and JNK and eckol suppressed the activation of p38. Therefore, the results of this study indicated that dieckol from E. cava might be applied as a drug candidate for the development of new generation therapeutic agents against AD.

The relationship between circulating neutrophil gelatinase-associated lipocalin and early alteration of metabolic parameters is associated with dietary saturated fat intake in non-diabetic Korean women.

Circulating neutrophil gelatinase-associated lipocalin (NGAL) is associated with obesity-related metabolic disorders. This study investigated the relationship between serum NGAL and early alteration of metabolic parameters in non-diabetic Korean women, particularly with respect to saturated fat (SFA) intake. Anthropometric parameters, fasting glycemic status, and levels of lipids, oxidative stress/inflammatory markers, and NGAL were measured in 82 non-diabetic Korean women [Super-healthy group (n=57) with 0 metabolic syndrome risk factor (MetS RF) and MetS-risk group (n=25) with MetS RF≥1]. Age, weight, waist circumference, blood pressure, fasting glucose, HbA1C, triglyceride, LDL and total-cholesterol, and NGAL levels were higher, and HDL-cholesterol was lower in the MetS-risk group than in the Super-healthy group. Age-adjusted serum NGAL levels were higher in the MetS-risk group than in the Super-healthy group. NGAL increased proportionally with increase in MetS RFs (p=0.038) and correlated positively with BMI, triglycerides, LDL- and total-cholesterol, interleukin-6, white blood cell count, and neutrophil%, and negatively with HDL-cholesterol and superoxide dismutase activity. Serum NGAL levels positively correlated with SFA intake before and after adjustment (age and BMI). Serum NGAL levels were higher in high-SFA consumers [≥7g/day, ≥7% of total calorie intake (TCI)] than in low-SFA consumers (<7g/day, <7% of TCI). Serum NGAL levels were highest in the MetS-risk group consuming higher SFA and lowest in the Super-healthy group consuming lower SFA. However, serum NGAL did not significantly differ between the low-SFA consuming MetS-risk and Super-healthy groups. The relationship between circulating NGAL and early alteration of metabolic parameters is associated with dietary SFA intake in non-diabetic Korean women.

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.

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.

Low-FODMAP formula improves diarrhea and nutritional status in hospitalized patients receiving enteral nutrition: a randomized, multicenter, double-blind clinical trial.

BACKGROUND: Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are poorly absorbed, short-chain carbohydrates that play an important role in inducing functional gut symptoms. A low-FODMAP diet improves abdominal symptoms in patients with inflammatory bowel disease and irritable bowel syndrome. However, there were no study for the effect of FODMAP content on gastrointestinal intolerance and nutritional status in patients receiving enteral nutrition (EN). METHODS: In this randomized, multicenter, double-blind, 14-day clinical trial, eligible hospitalized patients receiving EN (n = 100) were randomly assigned to three groups; 84 patients completed the trial (low-FODMAP EN, n = 30; moderate-FODMAP EN, n = 28; high-FODMAP EN, n = 26). Anthropometric and biochemical parameters were measured; stool assessment was performed using the King's Stool Chart and clinical definition. RESULTS: Baseline values were not significantly different among the three groups. After the 14-day intervention, diarrhea significantly improved in the low-FODMAP group than in the moderate- and high-FODMAP groups (P < 0.05). King's Stool scores in diarrhea subjects were significantly and steadily reduced in the low-FODMAP group compared with the other two groups (P for time and EN type interaction <0.05). BMI increased significantly in the low- and high-FODMAP groups during the intervention (P < 0.05 for both), and showed a trend toward increasing in the moderate-FODMAP group (P < 0.10). Serum prealbumin increased significantly in all groups by 14-day; by 3-day, it had increased to the levels at 14-day in the low-FODMAP group. At 14-day, serum transferrin had increased significantly in the moderate-FODMAP group. In addition, subjects were classified by final condition (unimproved, normal maintenance, diarrhea only improved, constipation only improved, and recurrent diarrhea/constipation improved). Seventy-five percent of the diarrhea improved group consumed the low-FODMAP EN formula. 38.5 and 46.2% of recurrent diarrhea/constipation improved group consumed the low- and moderate-FODMAP EN respectively. BMI significantly increased in all groups except the unimproved. Prealbumin levels significantly increased in the diarrhea-improved and recurrent diarrhea/constipation groups at 3-day and continued by 14-day, and in the constipation-improved group at 14-day. Transferrin levels significantly increased in the diarrhea-improved and recurrent diarrhea/constipation groups at 14-day. CONCLUSION: Low-FODMAP EN may improve diarrhea, leading to improved nutritional status and facilitating prompt recovery from illness.

Age-related increase in alanine aminotransferase correlates with elevated levels of plasma amino acids, decanoylcarnitine, Lp-PLA2 Activity, oxidative stress, and arterial stiffness.

We investigated plasma metabolite profiles that correlated with age-related serum alanine aminotransferase (ALT) levels. The study included 602 healthy, nondiabetic subjects (aged 30-65 years); 393 individuals had normal ALT levels at baseline. Fifty-three (13.5%) individuals developed elevated ALT levels after 3 years. The remaining 340 subjects with normal ALT were matched to the elevated-ALT group (n = 53) for age, gender, BMI, fasting glucose, and ALT to form the control group (n = 53). At the 3-year follow-up, the elevated-ALT group exhibited greater increases in waist circumference, serum free fatty acid, ALT, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), bilirubin, plasma oxidized LDL, Lp-PLA2 activity, urinary 8-epi-prostaglandin F2α (8-epi-PGF2α), and brachial-ankle pulse-wave velocity (ba-PWV) compared to the control group after baseline adjustment. The elevated-ALT group exhibited greater increases in plasma l-valine (q = 0.036), l-leucine (q = 0.012), l-phenylalanine (q = 0.012), and decanoylcarnitine (q = 0.002). Mean ALT levels positively correlated with changes in these four metabolites, which correlated with changes in AST, GGT, Lp-PLA2 activity, urinary 8-epi-PGF2α, and ba-PWV. Mean ALT changes did not significantly correlate with HOMA-insulin resistance. These results suggest that increased plasma levels of l-valine, l-leucine, l-phenylalanine, and decanoylcarnitine precede insulin resistance during periods of elevated ALT. This metabolic disturbance coincides with enhanced risk factors for cardiovascular disease.

Macronutrients modified dietary intervention in the management of overweight/obese children and adolescents: a systematic review.

The prevalence of obesity in adults and children is rapidly increasing worldwide. Obesity is among the main causes of chronic diseases and various problems, including economic consequences and they can also be affected by genetic, environmental, psychological, and socioeconomic factors. Dietary modification is a well-known and important factor in weight control, in particular, dietary macronutrient composition, food selection, dietary patterns, and energy restriction can affect weight reduction. Therefore, this systematic review aims to provide basic evidence for identifying the optimal macronutrient composition for managing obesity in Korean children and adolescents. We searched literature through an international database, studies were selected using our eligibility criteria and quality was assessed via a risk of bias tool. In our results, several studies have demonstrated that dietary macronutrient modifications affect body composition and metabolic markers in children and adolescents. In contrast, hypocaloric diets, regardless of macronutrient composition, are reportedly effective for weight loss in obese children. However, these findings were based on intervention studies that examined the association between dietary macronutrient composition and obesity in non-Korean children and adolescents. Therefore, in the future, more intervention studies are needed to elucidate this relationship and evidence between macronutrients and obesity in Korean children and adolescents.

Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia.

Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia accompanied by memory loss and depression. The direct pathways and specific mechanisms in the central nervous system (CNS) for addressing fatty acid imbalances in MetS have not yet been fully elucidated. Among polyunsaturated acids, linoleic acid (LA, n6-PUFA) and α-linolenic acid (ALA, n3-PUFA), which are two essential fatty acids that should be provided by food sources (e.g., vegetable oils and seeds), have been reported to regulate various cellular mechanisms including apoptosis, inflammatory responses, mitochondrial biogenesis, and insulin signaling. Furthermore, inadequate intake of LA and ALA is reported to be involved in neuropathology and neuropsychiatric diseases as well as imbalanced metabolic conditions. Herein, we review the roles of LA and ALA on metabolic-related dementia focusing on insulin resistance, dyslipidemia, synaptic plasticity, cognitive function, and neuropsychiatric issues. This review suggests that LA and ALA are important fatty acids for concurrent treatment of both MetS and neurological problems.

Gut microbiota and their relationship with circulating adipokines in an acute hepatic encephalopathy mouse model induced by surgical bile duct ligation.

Background and aims: Various studies have shown the importance of the gut microbiota in human health. However, little is known about gut microbiome patterns and their effect on circulating adipo-myokine levels in hepatic encephalopathy (HE). We investigated the relationship between the gut microbiota and adipo-myokine levels using a mouse model of HE induced by surgical bile duct ligation (BDL). Methods and results: Wild-type C57BL/6J mice were subjected to sham surgery or BDL. Severe body weight loss, suppressed feed intake, and liver failure were observed in BDL mice compared with sham control mice. Additionally, changes in gut microbial communities and serum adipo-myokine levels were noted in BDL mice. In the BDL mouse gut, we identified 15 differentially abundant taxa including the phylum Verrucomicrobiota, the classes Actinomycetes and Verrucomicrobiae, the order Verrucomicrobiales, the families Akkermansiaceae, Bacteroidaceae, Rikenellaceae, and Oscillospiraceae, the genera Alistipes, Akkermansia, Muribaculum, and Phocaeicola, and the species Akkermansia muciniphila, Alistipes okayasuensis, and Muribaculum gordoncarteri by LEfSe analysis (LDA score≥4.0). Higher levels of certain adipo-myokines such as BDNF were detected in the serum of BDL mice. Spearman correlation analysis revealed that certain adipo-myokines (e.g., FSTL1) were positively correlated with the class Actinomycetes, the family Rikenellaceae, the genus Alistipes, and the species Alistipes okayasuensis. Interestingly, A. okayasuensis and M. gordoncarteri, recently isolated microbes, showed richness in the gut of BDL mice and demonstrated positive correlations with adipo-myokines such as FGF21. Conclusions: Overall, our results suggest that alteration of the gut microbiota in patients with HE may be closely correlated to the levels of adipo-myokines in the blood.

Oligonol enhances brain cognitive function in high-fat diet-fed mice.

Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, is well recognized for its antioxidant properties, blood glucose regulation, and fat mass reduction capability. However, its effect on the central nervous system remains unclear. Here, we investigated the effects of oligonol on brain in a high-fat diet (HFD) fed mouse model, and SH-SY5Y neuronal cells and primary cultured cortical neuron under insulin resistance conditions. HFD mice were orally administered oligonol (20 mg/kg) daily, and SH-SY5Y cells and primary cortical neurons were pretreated with 500 ng/mL oligonol under in vitro insulin resistance conditions. Our findings revealed that oligonol administration reduced blood glucose levels and improved spatial memory function in HFD mice. In vitro data demonstrated that oligonol protected neuronal cells and enhanced neural structure against insulin resistance. We confirmed RNA sequencing in the oligonol-pretreated insulin-resistant SH-SY5Y neuronal cells. Our RNA-sequencing data indicated that oligonol contributes to metabolic signaling and neurite outgrowth. In conclusion, our study provides insights into therapeutic potential of oligonol with respect to preventing neuronal cell damage and improving neural structure and cognitive function in HFD mice.

Follow-ups of metabolic, inflammatory and oxidative stress markers, and brachial-ankle pulse wave velocity in middle-aged subjects without metabolic syndrome.

This study investigates the association among metabolic risk factors, inflammatory and oxidative stress markers, and brachial-ankle pulse wave velocity (ba-PWV). We conducted a 3-year longitudinal, observational study of 288 middle-aged adults not meeting the criteria for metabolic syndrome (MetS) at the initial screening. We measured metabolic risk factors, inflammatory and oxidative stress markers, and ba-PWV. Within the 3-year study period, 15.6% (45 out of 288) of participants developed MetS. At the 3-year follow-up, patients were categorized as those with MetS (n = 45) and those without MetS (n = 243). Patients with MetS had significantly unfavorable initial measurements of baseline body mass index (BMI), waist circumference (WC), blood pressure (BP), triglyceride (TG), high-density lipoprotein (HDL)-cholesterol, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, and ba-PWV. After 3 years, participants without MetS showed significant increases in WC, diastolic BP (DBP), total- and low-density lipoprotein (LDL)-cholesterol, malondialdehyde (MDA), oxidized-LDL (ox-LDL), and ba-PWV and a significant decrease in HDL-cholesterol and free fatty acids (FFA). Subjects who developed MetS showed significant increases in BMI, WC, BP, TG, glucose, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), MDA, ox-LDL, and ba-PWV and a significant decrease in HDL-cholesterol. Changes in BMI, WC, BP, TG, HDL-cholesterol, glucose, HOMA-IR index, FFA, C-reactive protein (P = .022), IL-6 (P = .004), leukocyte count (P < .001), MDA (P = .002), ox-LDL (P = .015), and ba-PWV (P = .001) differed significantly between the two groups after adjustment for baseline values. Changes in ba-PWV were positively correlated with the changes in systolic and DBP, total-cholesterol, glucose, leukocyte count, and MDA. The age-related increase in arterial stiffness is greater in the presence of MetS with higher levels of inflammatory and oxidative stress markers.

The Synergistic Effect of Dietary Acid Load Levels and Cigarette Smoking Status on the Risk of Chronic Obstructive Pulmonary Disease (COPD) in Healthy, Middle-Aged Korean Men.

We investigated whether cigarette smoking and dietary acid load (DAL) are associated with a risk of chronic obstructive pulmonary disease (COPD) in healthy, middle-aged Korean men. Healthy men without diagnosed chronic disease (aged 40-64 years) from the KNHANES-VI (2013-2015) were included in the analysis (n = 774) and were subdivided by smoking status and DAL levels, as estimated using the quartile of net endogenous acid production (NEAP). The current smokers tended to have a higher risk of COPD than the never-smokers before and after adjustment. When divided by the DAL quartile, the Q4 group tended to have a higher risk of COPD than the Q1 group. Additionally, the current smokers with lower (Q2), modest (Q3), and the highest NEAP scores (Q4) showed risks of COPD that were more than fourfold higher than those of the never-smokers with the lowest NEAP scores (Q1). The ex-smokers with higher NEAP scores (Q3 and Q4) showed risks of COPD that were more than fourfold higher than those of the Q1 group. Interestingly, the risk of COPD was also more than sixfold higher in the never-smokers with the highest NEAP scores compared to that in the Q1 group. The NEAP scores and smoking status synergistically increased the risk of COPD in healthy, middle-aged Korean men. This suggests that DAL levels are an important factor in the prevention and management of COPD.

The association between dietary sodium intake and obesity in adults by sodium intake assessment methods: a review of systematic reviews and re-meta-analysis.

BACKGROUND/OBJECTIVES: The scientific evidence of a sodium-obesity association is limited by sodium intake assessments. Our specific aim is to synthesize the association between dietary sodium intake and obesity across the sodium intake assessments as evidenced by systematic reviews in adults. SUBJECTS/METHODS: A systematic search identified systematic reviews comparing the association of dietary sodium intakes with obesity-related outcomes such as body mass index (BMI), body weight, waist circumference, and risk of (abdominal) obesity. We searched PubMed on October 24, 2022. To assess the Risk of Bias in Systematic Reviews (ROBIS), we employed the ROBIS tool. RESULTS: This review included 3 systematic reviews, consisting of 39 unique observational studies (35 cross-sectional studies and 4 longitudinal studies) and 15 randomized controlled trials (RCTs). We found consistently positive associations between dietary sodium intake and obesity-related outcomes in cross-sectional studies. Studies that used 24-h urine collection indicated a greater BMI for those with higher sodium intake (mean difference = 2.27 kg/m2; 95% confidence interval [CI], 1.59-2.51; P < 0.001; I2 = 77%) compared to studies that used spot urine (mean difference = 1.34 kg/m2; 95% CI, 1.13-1.55; P < 0.001; I2 = 95%) and dietary methods (mean difference = 0.85 kg/m2; 95% CI, 0.1-1.51; P < 0.05; I2 = 95%). CONCLUSIONS: Quantitative synthesis of the systematic reviews has shown that cross-sectional associations between dietary sodium intake and obesity outcomes were substantially different across the sodium intake assessments. We need more high-quality prospective cohort studies and RCTs using 24-h urine collection to examine the causal effects of sodium intake on obesity.

Minor alleles in the FTO SNPs contributed to the increased risk of obesity among Korean adults: meta-analysis from nationwide big data-based studies.

BACKGROUND/OBJECTIVES: Many studies have revealed an association between fat mass and the obesity-related gene (FTO) and obesity. On the other hand, no meta-analysis was conducted with data from only Koreans. Therefore, this study performed a meta-analysis using Korean data to provide evidence for the association between FTO single nucleotide polymorphisms (SNPs) and the risk of obesity among Korean adults. SUBJECT/METHODS: Meta-analysis was finally conducted with data extracted from seven datasets of four studies performed on Korean adults after the screening passed. Five kinds of FTO SNPs (rs9939609, rs7193144, rs9940128, rs8050136, and rs9926289) were included, and the relationship between FTO SNPs and body mass index (BMI) was investigated using linear regression with an additive model adjusted for covariants, such as age, sex, and area. RESULTS: The minor alleles of FTO SNPs were associated with increased BMI (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.21-1.42). In sub-group analysis, FTO rs9939609 T>A was significantly associated with BMI (OR, 1.23; 95% CI, 1.06-1.42). The other FTO SNPs together were significantly associated with BMI (OR, 1.37; 95% CI, 1.25-1.49). The publication bias was not observed based on Egger's test. CONCLUSIONS: This meta-analysis showed that minor alleles in the FTO SNPs were significantly associated with an increased BMI among Korean adults. This meta-analysis is the first to demonstrate that minor alleles in the FTO SNPs contribute significantly to the increased risk of obesity among Korean adults using data from a Korean population.

Oligonol ameliorates liver function and brain function in the 5 × FAD mouse model: transcriptional and cellular analysis.

Alzheimer's disease (AD) is a common neurodegenerative disease worldwide and is accompanied by memory deficits, personality changes, anxiety, depression, and social difficulties. For treatment of AD, many researchers have attempted to find medicinal resources with high effectiveness and without side effects. Oligonol is a low molecular weight polypeptide derived from lychee fruit extract. We investigated the effects of oligonol in 5 × FAD transgenic AD mice, which developed severe amyloid pathology, through behavioral tests (Barnes maze, marble burying, and nestle shredding) and molecular experiments. Oligonol treatment attenuated blood glucose levels and increased the antioxidant response in the livers of 5 × FAD mice. Moreover, the behavioral score data showed improvements in anxiety, depressive behavior, and cognitive impairment following a 2-month course of orally administered oligonol. Oligonol treatment not only altered the circulating levels of cytokines and adipokines in 5 × FAD mice, but also significantly enhanced the mRNA and protein levels of antioxidant enzymes and synaptic plasticity in the brain cortex and hippocampus. Therefore, we highlight the therapeutic potential of oligonol to attenuate neuropsychiatric problems and improve memory deficits in the early stage of AD.

The association of specific metabolites of lipid metabolism with markers of oxidative stress, inflammation and arterial stiffness in men with newly diagnosed type 2 diabetes.

OBJECTIVE: To determine whether circulating metabolic intermediates are associated with inflammation, oxidative stress and arterial stiffness in men with newly diagnosed type 2 diabetes and investigate the circulating metabolic intermediates that may predict the risk of developing diabetes. RESEARCH DESIGN AND METHODS: Men with newly diagnosed type 2 diabetes (n = 26) and age- and body mass index-matched nondiabetic men (n = 27) were included. We measured inflammatory and oxidative markers and arterial stiffness by brachial-ankle pulse wave velocity (ba-PWV). Metabolomic profiling was analysed with ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry. RESULTS: Diabetic men showed higher circulating levels of glucose, triglyceride, oxidized low-density lipoprotein (LDL), high-sensitivity C-reactive protein, interleukin (IL)-6, tumour necrosis factor-alpha (TNF-α), homeostasis model assessment-insulin resistance, urinary 8-epi-prostaglandin F(2α) (8-epi-PGF(2α)) and ba-PWV than nondiabetic men. In plasma, 19 metabolites including three amino acids, eight acylcarnitines, six lysophosphatidylcholines (lysoPCs), and two lysophosphatidylethanolamines (lysoPEs; C18:2 and C22:6) significantly increased in diabetes men, whereas serine and lysoPE (C18:1) decreased. Decanoyl carnitine, lysoPCs (C14:0, C16:1, C18:1 and C22:6) and lysoPE (C18:1) with variable importance in the projection values >1·0 were major plasma metabolites that distinguished nondiabetic and diabetic men. Decanoyl carnitine positively correlated with oxidized LDL, 8-epi-PGF(2α), IL-6, TNF-α and ba-PWV. ba-PWV correlated positively with lysoPCs C14:0 and C16:1, and negatively with lysoPE C18:1. 8-epi-PGF(2α) correlated positively with lipoprotein-associated phospholipase A(2), ba-PWV and lysoPCs (C14:0 and C16:1). The receiver operating characteristic curve estimation suggested that decanoyl carnitine and lysoPC (C14:0) are the best metabolites for predicting the risk of developing diabetes. CONCLUSIONS: Circulating lipid-related intermediate metabolites can be closely associated with inflammation, oxidative stress and arterial stiffness in early diabetes.

Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The reported health benefits of Korean red ginseng (KRG) include antioxidant, antitumor, antimutagenic, and immunomodulatory activities; however, the effects on oxidative stress have not yet been evaluated. Therefore, we assessed the effect of KRG on antioxidant enzymes and oxidative stress markers in humans. METHODS: We conducted a randomized, double-blind, placebo-controlled study with three groups, including placebo, low-dose (3 g/day), and high-dose (6 g/day), which were randomly assigned to healthy subjects aged 20-65 years. Lymphocyte DNA damage, antioxidative enzyme activity, and lipid peroxidation were assessed before and after the 8-week supplementation. RESULTS: Fifty-seven subjects completed the protocol. Plasma superoxide dismutase (SOD) activity after the 8-week KRG supplementation was significantly higher in the low-and high-dose groups compared to baseline. Plasma glutathione peroxidase (GPx) and catalase activities were also increased after the high-dose supplementation. Furthermore, the DNA tail length and tail moment were significantly reduced after the supplementation (low-dose and high-dose), and plasma oxidized low-density lipoprotein (LDL) levels were reduced in low-dose and high-dose groups, but increased in the placebo group. The net changes in oxidized LDL after the supplementation differed significantly between both KRG supplementation groups and the placebo group. Net changes in GPx, SOD and catalase activities, and DNA tail length and tail moment were significantly different between the high-dose group and the placebo group. Additionally, the net changes in urinary 8-epi-PGF(2α) were significantly different between the KRG supplementation groups and the placebo group. CONCLUSIONS: KRG supplementation may attenuate lymphocyte DNA damage and LDL oxidation by upregulating antioxidant enzyme activity.

Beneficial immunostimulatory effect of short-term Chlorella supplementation: enhancement of natural killer cell activity and early inflammatory response (randomized, double-blinded, placebo-controlled trial).

BACKGROUND: In vitro and animal studies have demonstrated that Chlorella is a potent biological response modifier on immunity. However, there were no direct evidences for the effect of Chlorella supplementation on immune/inflammation response in healthy humans. METHODS: This study was designed for an 8-week randomized, double-blinded, placebo-controlled trial: 5g of Chlorella (n=23) or Placebo (n=28) as form of tablets. Mainly, cytotoxic activities of Natural killer (NK) cells and serum concentrations of interferon-γ, interleukin-1ß and interleukin-12 were measured. RESULTS: After the 8-week, serum concentrations of interferon-γ (p<0.05) and interleukin-1ß (p<0.001) significantly increased and that of interleukin-12 (p<0.1) tended to increase in the Chlorella group. The increments of these cytokines after the intervention were significantly bigger in the Chlorella group than those in the placebo group. In addition, NK cell activities (%) were significantly increased in Chlorella group, but not in Placebo group. The increments of NK cell activities (%) were also significantly bigger in the Chlorella group than the placebo group. Additionally, changed levels of NK cell activity were positively correlated with those of serum interleukin-1ß (r=0.280, p=0.047) and interferon-γ (r=0.271, p<0.005). Signficantly positive correlations were also observed among the changed levels of serum cytokines; between interferon-γ and interleukin-1ß (r=0.448, p<0.001), between interleukin-12 and interleukin-1ß (r=0.416, p=0.003) and between interleukin-12 and interferon-γ (r=0.570, p<001). CONCLUSION: These results may suggest a beneficial immunostimulatory effect of short-term Chlorella supplementation which enhances the NK cell activity and produces interferon-γ and interleukin-12 as well as interleukin-1ß, the Th-1 cell-induced cytokines in healthy people.