Associations of Meat and Fish/Seafood Intake with All-Cause and Cause-Specific Mortality from Three Prospective Cohort Studies in Korea.

SCOPE: Animal protein intake among Koreans has recently increased. However, there is limited evidence on the association of meat and fish/seafood intake and mortality. METHODS AND RESULTS: This study uses three representative prospective cohorts in Korea and 134,586 eligible participants are selected. Food intake is assessed using a food frequency questionnaire. Outcomes are classified as death from cardiovascular disease (CVD), cancer, and all-causes. Red meat intake shows a marginally negative association with all-cause mortality in the median intake group and a positive association in the highest intake group. Processed meat intake in the highest quintile group is positively associated with all-cause mortality compared to that of the lowest quintile group. Fish intake in the highest quintile group is negatively associated with CVD mortality in men, and all-cause mortality in women, compared to those in the lowest quintile group, while processed fish intake has unfavorable effects on mortality. In addition, substitution of one serving per week of red and processed meat, and processed fish with fish is negatively associated with all-cause and CVD mortality. CONCLUSION: Reduction of red and processed meat, and processed fish consumption or replacement of these foods with fish may be beneficial for longevity in Korean adults.

Umbilicaria esculenta Extract Exhibits Antiwrinkle Activity by Suppressing ErbB2 Phosphorylation.

Umbilicaria esculenta (UE), an edible lichen, is widespread in northeast Asian countries, including China, Japan, and Korea. In the present study, we examined the antiwrinkle activity of UE. We observed that the UE extract (UEE) suppressed ultraviolet (UV)-induced matrix metalloprotein-1 (MMP-1) expression and reactive oxygen species (ROS) generation in a human keratinocyte cell line (HaCaT) and human skin tissue. In addition, UEE reversed the UV-induced decrease in collagen in the human skin tissue. Excessive and chronic UV exposure is a key factor underlying skin wrinkle formation via MMP-1 expression. As treatment with UEE disrupted the UV-activated mitogen-activated protein kinase (MAPK) signaling pathway, we applied an antibody array to unveil the underlying mechanism of UEE. Interestingly, UEE treatment inhibited ErbB2 phosphorylation, but not epidermal growth factor receptor phosphorylation, a heterodimerization partner with ErbB2. Furthermore, UEE treatment enhanced UV-suppressed phosphatase activity via ROS suppression. Collectively, our findings indicate that UEE enhances ErbB2 dephosphorylation to suppress UV-induced MMP-1 expression.

Anti-obesity effects of medicinal plants from Asian countries and related molecular mechanisms: a review.

Medicinal plants have been used as an alternative medicine for obesity prevention, and Asian countries, which are major habitats of various medicinal plant species, have traditionally used these medicines for centuries. Obesity is a global health problem caused by excessive fat accumulation linked to abnormal lipid metabolism, such as adipogenesis, lipogenesis, and lipolysis. Accordingly, the effects of medicinal plants on obesity-related mechanisms and biomarkers have been evaluated in various experimental studies. For example, adipogenesis and lipogenesis are regulated by several transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, and fatty acid synthase. Moreover, activation of the adenosine monophosphate-activated protein kinase pathway is accompanied by promotion of lipolysis. However, few reports have consolidated studies of the effects of various Asian medicinal plants on obesity and related mechanisms. Therefore, in this review, we examined the associations of medicinal plants originating from Asian countries with obesity and discussed the related mechanisms and biomarkers from in vitro and in vivo studies.

Anacardic Acid Suppresses Adipogenesis Through Inhibition of the Hsp90/Akt Signaling Pathway in 3T3-L1 Preadipocytes.

Anacardic acid (AA), a major component of cashew nut shell liquid, has extensive bioactivities. However, little is known about its antiadipogenic properties or the mechanism that underpins them. The aim of this study was to investigate the effect of AA on 3T3-L1 preadipocyte differentiation and its mechanisms of action. AA inhibits lipid accumulation during adipogenesis in 3T3-L1 preadipocyte (IC50 = 25.45 µM). AA abrogates mRNA expressions of the genes implicated in lipogenesis and their transcription factors, especially Pparg and Cebpa. Furthermore, antibody microarray and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results showed that the proteins implicated in the Akt signaling pathway were most likely altered by AA. Notably, upon AA treatment, heat shock protein 90 (Hsp90), a positive regulator of Akt, was decreased, resulting in Akt degradation. These findings indicate that AA, a natural product that acts as a Hsp90/Akt signaling inhibitor, may be a possible antiadipogenic agent.

Butein Synergizes with Statin to Upregulate Low-Density Lipoprotein Receptor Through HNF1α-Mediated PCSK9 Inhibition in HepG2 Cells.

Downregulation of the low-density lipoprotein (LDL) receptor (LDLR) can lead to hypercholesterolemia and related conditions, including cardiovascular diseases. Statins are a class of LDL cholesterol-lowering agents and are best-selling medications for patients at high risk of developing cardiovascular diseases. Indeed, statins upregulate LDLR and proprotein convertase subtilisin/kexin type 9a (PCSK9), leading to LDLR lysosomal degradation, which interferes with the attenuation of hypercholesterolemia. In the present study, butein was found to decrease extracellular PCSK9 levels by reducing its mRNA expression, which was attributable to butein-mediated downregulation of HNF1α in HepG2 cells. Butein-mediated PCSK9 inhibition further reversed LDLR protein synthesis inhibition, which possibly occurred through butein-mediated inhibition of LDLR degradation. When treated as a combination of butein and a statin, butein reduced statin-mediated enhancement of PCSK9 protein expression. This resulted in a synergistic enhancement of LDLR protein expression, whereas butein alone marginally increased LDLR protein expression. These findings suggest that butein, a novel PCSK9 inhibitor, may be a potential alternative or adjunct to statin treatment.

Ethanol Extract of Ligularia fischeri Inhibits the Lipopolysaccharide-Induced Inflammatory Response by Exerting Anti-Histone Acetyltransferase Activity to Negatively Regulate p65.

Histone acetyltransferase (HAT) activity is well established to regulate inflammatory responses. In contrast, the mechanisms by which natural nutritional extracts influence epigenetic mechanisms to regulate inflammation have not yet been thoroughly investigated. Thus, in the present study, we observed that the anti-HAT activity exerted by an ethanol extract of Ligularia fischeri (ELF) inhibited inflammation. Specifically, we used a cell-free system to show that ELF attenuates HAT activity. We also demonstrated that ELF decreases lipopolysaccharide (LPS)-induced HAT mRNA and protein expression levels in Raw 264.7 cells, and thereby attenuates inflammation-induced patterns of hyperacetylation at nonhistone and histone-H4 proteins. Interestingly, we found that ELF blocked p65 translocation in LPS-stimulated Raw 264.7 cells by attenuating acetylation at lysine residue 310 of p65. Finally, we investigated whether ELF reduces the inflammatory cytokines, IL-6, IL-1ß, and TNFα, using its HAT inhibitor activity. Taken together, these results suggest that ELF negatively regulates inflammatory responses by inhibiting HATs and HAT activity.

Dietary Patterns May Be Nonproportional Hazards for the Incidence of Type 2 Diabetes: Evidence from Korean Adult Females.

This study aimed to examine the association between the incidence of type 2 diabetes and various risk factors including dietary patterns based on the rigorous proportional hazards assumption tests. Data for 3335 female subjects aged 40-69 years from the Korea Genome and Epidemiology Study were used. The assumption of proportional hazards was tested using the scaled Schoenfeld test. The stratified Cox regression was used to adjust the nonproportionality of diabetic risk factors, and the regression was adjusted for potential confounding variables, such as age, marital status, physical activity, drinking, smoking, BMI, etc. Metabolic syndrome and meat and fish pattern variables were positively associated with diabetes. However, dietary patterns and metabolic syndrome variables violated the proportional hazards assumption; therefore, the stratified Cox regression with the interaction terms was applied to adjust the nonproportionality and to allow the possible different parameters over each stratum. The highest quartile of meat and fish pattern was associated with diabetes only in subjects aged over 60 years. Moreover, subjects who were obese and had metabolic syndrome had higher risk in bread and snacks (HR: 1.85; 95% CI: 1.00-3.40) and meat and fish pattern (HR: 1.82; 95% CI: 1.01-3.26), respectively. In conclusion, a quantitative proportional hazards assumption test should always be conducted before the use of Cox regression because nonproportionality of risk factors could induce limited effect on diabetes incidence.

Genome-wide analysis of DNA methylation identifies novel differentially methylated regions associated with lipid accumulation improved by ethanol extracts of Allium tubersosum and Capsella bursa-pastoris in a cell model.

Hepatic steatosis is the most common chronic liver disease in Western countries. Both genetic and environmental factors are known as causes of the disease although their underlying mechanisms have not been fully understood. This study investigated the association of DNA methylation with oleic acid-induced hepatic steatosis. It also examined effects of food components on DNA methylation in hepatic steatosis. Genome-wide DNA methylation of oleic acid (OA)-induced lipid accumulation in vitro cell model was investigated using reduced representation bisulfite sequencing. Changes of DNA methylation were also analyzed after treatment with food components decreasing OA-induced lipid accumulation in the model. We identified total 81 regions that were hypermethylated by OA but hypomethylated by food components or vice versa. We determined the expression of seven genes proximally located at the selected differentially methylated regions. Expression levels of WDR27, GNAS, DOK7, MCF2L, PRKG1, and CMYA5 were significantly different between control vs OA and OA vs treatment with food components. We demonstrated that DNA methylation was associated with expression of genes in the model of hepatic steatosis. We also found that food components reversely changed DNA methylation induced by OA and alleviated lipid accumulation. These results suggest that DNA methylation is one of the mechanisms causing the hepatic steatosis and its regulation by food components provides insights that may prevent or alleviate lipid accumulation.

Anti-tumour effects of beta-sitosterol are mediated by AMPK/PTEN/HSP90 axis in AGS human gastric adenocarcinoma cells and xenograft mouse models.

We investigated the anti-cancer effects of beta-sitosterol (BS), a plant-derived sterol in AGS human gastric adenocarcinoma cells and xenograft mouse models. BS significantly reduced cell viability by inducing apoptosis in AGS adenocarcinoma cells. This was accompanied by the formation of apoptotic bodies, as detected by Annexin V, caspase 3/7 activity, and MitoPotential assay. BS stimulated phosphatase and tensin homolog (PTEN) and phospho-AMP-activated protein kinase (p-AMPK) expression. Pharmacological inhibitors or siRNA were used to further analyse the relationship between the two proteins. AMPK was found to represent a likely upstream regulator of PTEN. Additionally, two-dimensional gel electrophoresis was used to identify related proteins in the treatment of BS. The decrease of Hsp90 protein by BS was observed. Induction of PTEN protein and reduction of Hsp90 was mediated by AICAR, an AMPK activator, indicating that AMPK is necessary for PTEN and Hsp90 expression. Additionally, BS was found to be effective through the regulation of cancer biomarker. Furthermore, BS suppressed tumour growth without toxicity in the AGS xenograft mouse models-. Taken together, the present results demonstrate that BS exerts anti-cancer effects in AGS cells and xenograft mouse models by mediating AMPK, PTEN, and Hsp90.

Meat and milk intake in the rice-based Korean diet: impact on cancer and metabolic syndrome.

Over a few decades, Korean diet has changed from traditional diet, mainly composed of rice and vegetables, to Westernised diet rich, in meat and milk, along with the economic development and globalisation. Increasing prevalence of diet-related chronic diseases such as cancer and metabolic syndrome (MetS) is becoming a heavy burden to society and requires further attention. In this review, the association of meat and milk consumption with cancer and MetS among Koreans was discussed. Previous meta-analyses showed that meat intake was positively associated with increased risk of cancers, especially colon, as well as obesity and type 2 diabetes mellitus, and that the intake of milk and dairy products was negatively associated with colorectal cancer, obesity, and type 2 diabetes mellitus, based on studies conducted mostly in Western countries. In Korea and other Asian countries, the association of meat and milk intake with cancers were inconclusive and varied by types of cancers. Conversely, milk intake was negatively associated with MetS risk as reported in Western countries. The difference in results between Korea and Western countries might come from the differences in dietary patterns and study designs. Most Koreans still maintain traditional dietary pattern, although rapid change towards Westernised diet is underway among the younger age group. Randomised clinical trials or prospective cohort studies with consideration of combined effects of various dietary factors in Korea and other Asian countries are needed to elucidate the impact of meat and milk or related dietary patterns in their diet.