Skipping breakfast is associated with diet quality and metabolic syndrome risk factors of adults

The aim of the present study was to assess the effects of skipping breakfast on diet quality and metabolic disease risk factors in healthy Korean adults. Subjects included 415 employees (118 men, 297 women; 30-50 years old) of Jaesang Hospital in Korea and their acquaintances. Data collected from each subject included anthropometric measurements, 3-day dietary intake, blood pressure, and blood analyses. The subjects were classified into three groups based on the number of days they skipped breakfast: 'Regular breakfast eater', 'Often breakfast eater', or 'Rare breakfast eater'. Participants in the 'Rare breakfast eater' group consumed less rice, potatoes, kimchi, vegetables, fish and shellfish, milk and dairy products, and sweets than did participants in the other two groups (P for trend < 0.05) and ate more cookies, cakes, and meat for dinner (P for trend < 0.05). Participants in the 'Rare breakfast eater' group consumed less daily energy, fat, dietary fiber, calcium, and potassium than did participants in the other groups (P for trend < 0.05). The percent energy from carbohydrates was lower and fat intake was higher in the 'Rare breakfast eater' group than in the other groups (P for trend < 0.01). When diets were compared using the Acceptable Macronutrient Distribution Range for Koreans, 59.1% of subjects in the 'Rare breakfast eater' group consumed more energy from fat compared with the other two groups (P < 0.005). According to the Estimated Average Requirements for Koreans, intake of selected nutrients was lower in the 'Rare breakfast eater' group than in the other two groups (P < 0.05). The risk of elevated serum triglycerides was decreased in the 'Rare breakfast eater' group (OR, 0.3 [0.1-1.0], P for trend = 0.0232). We conclude that eating breakfast regularly enhances diet quality, but may increase the risk of elevated serum triglycerides

A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.

Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases

Breakfast patterns are associated with metabolic syndrome in Korean adults

The Korean diet, including breakfast, is becoming more Western, which could increase the risk of metabolic syndrome. Our aim was to assess whether breakfast patterns are associated with risk for metabolic syndrome in Korean adults. The study subjects (n = 371; 103 men, 268 women) were employees of Jaesang Hospital in Korea and their acquaintances, and all subjects were between 30 and 50 years old. The data collected from each subject included anthropometric measurements, three-day food intake, blood pressure (BP) and blood analyses. The three breakfast patterns identified by factor analysis were "Rice, Kimchi and Vegetables", "Potatoes, Fruits and Nuts" and "Eggs, Breads and Processed meat". The "Rice, Kimchi and Vegetables" pattern scores were positively correlated with systolic (SBP) and diastolic blood pressure (DBP) measurements in men (P < 0.05) and with serum triglyceride (TG) levels in women (P < 0.05). The "Eggs, Breads and Processed meat" pattern scores correlated positively with weight, body mass index (P < 0.05) and serum TGs (P < 0.01) in men. The "Potatoes, Fruits and Nuts" pattern was associated with lower risk of elevated BP (OR 0.49, 95% CI 0.28-0.88) and fasting glucose levels (OR 0.51, 95% CI 0.26-1.00). In contrast, the "Eggs, Breads and Processed meat" pattern was associated with increased risk of elevated TGs (OR 2.06, 95% CI 1.06-3.98). Our results indicate that reducing the consumption of eggs, western grains and processed meat while increasing fruit, nut and vegetable intake for breakfast could have beneficial effects on decreasing metabolic syndrome risk in Korean adults

Recent Advances in Synthesis of 4-Arylcoumarins

4-Arylcoumarins (4-aryl-2H-1-benzopyran-2-one), also known as neoflavones, comprise a minor subclass of naturally occurring flavonoids. Because of their broad-spectrum biological activities, arylcoumarins have been attracting the attention of the organic and medicinal chemistry communities, and are considered as an important privileged scaffold. Since the development of Pechmann condensation, a classical acid-catalyzed condensation between phenol and &beta;-keto-carboxylic acid, several versatile and efficient synthetic approaches for 4-arylcoumarins have been reported. This review summarizes recent advances in the synthesis of the 4-arylcoumarin scaffold by classifying them based on the final bond-formation type. In particular, synthetic methods executed under mild and highly efficient conditions, such as solvent-free reactions and transition metal catalysis, are highlighted

Assessment of Metabolic Interaction between Repaglinide and Quercetin via Mixed Inhibition in the Liver: In Vitro and In Vivo

Repaglinide (RPG), a rapid-acting meglitinide analog, is an oral hypoglycemic agent for patients with type 2 diabetes mellitus. Quercetin (QCT) is a well-known antioxidant and antidiabetic flavonoid that has been used as an important ingredient in many functional foods and complementary medicines. This study aimed to comprehensively investigate the effects of QCT on the metabolism of RPG and its underlying mechanisms. The mean (range) IC50 of QCT on the microsomal metabolism of RPG was estimated to be 16.7 (13.0–18.6) μM in the rat liver microsome (RLM) and 3.0 (1.53–5.44) μM in the human liver microsome (HLM). The type of inhibition exhibited by QCT on RPG metabolism was determined to be a mixed inhibition with a Ki of 72.0 μM in RLM and 24.2 μM in HLM as obtained through relevant graphical and enzyme inhibition model-based analyses. Furthermore, the area under the plasma concentration versus time curve (AUC) and peak plasma concentration (Cmax) of RPG administered intravenously and orally in rats were significantly increased by 1.83- and 1.88-fold, respectively, after concurrent administration with QCT. As the protein binding and blood distribution of RPG were observed to be unaltered by QCT, it is plausible that the hepatic first-pass and systemic metabolism of RPG could have been inhibited by QCT, resulting in the increased systemic exposure (AUC and Cmax) of RPG. These results suggest that there is a possibility that clinically significant pharmacokinetic interactions between QCT and RPG could occur, depending on the extent and duration of QCT intake from foods and dietary supplements

Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis

Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can be categorized prudently as chiral sources, devices, and inducers. This review specifically examines recent advances in substrate-controlled asymmetric reactions induced by the chirality of α-amino acid templates in natural product synthesis research and related areas

Eletrophilic Chemistry of Tranilast Is Involved in Its Anti-Colitic Activity via Nrf2-HO-1 Pathway Activation

Tranilast (TRL), a synthetic derivative of a tryptophan metabolite, is an anti-allergic drug used to treat bronchial asthma. We investigated how TRL activated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)-hemeoxygenase-1 (HO-1) pathway based on the electrophilic chemistry of the drug and whether TRL activity contributed to the treatment of rat colitis. In human colon carcinoma cells, TRL activated Nrf2, as represented by an increase in nuclear Nrf2 and induction of Nrf2-dependent luciferase and, subsequently, HO-1, a target gene product of Nrf2. TRL activation of Nrf2 and induction of HO-1 were completely prevented by chemical reduction of the electrophilic functional group (α, β-unsaturated carbonyl group) in the drug. In parallel, TRL was reactive with the nucleophilic thiol group in N-acetylcysteine, forming a covalent adduct. Moreover, TRL, but not reduced TRL, binds to Kelch-like ECH-associated protein 1 (KEAP1), releasing Nrf2. TRL administration ameliorated colonic damage and inflammation in rats with dinitrobenzene sulfonic acid-induced colitis, which was partly compromised by the chemical reduction of TRL or co-treatment with an HO-1 inhibitor. Our results suggest that TRL activated the Nrf2-HO-1 pathway via covalent binding to KEAP1, partly contributing to TRL amelioration in rat colitis