Amino acid intake with protein food source and incident dyslipidemia in Korean adults from the Ansan and Ansung Study and the Health Examinee Study.

Background: Dyslipidemia is a major risk factor for cardiovascular diseases and appropriate intake of amino acids may be helpful for the management of dyslipidemia. However, evidence of an association between amino acid intake and dyslipidemia in Korean adults is limited. Objective: The purpose of this study was to investigate how the incidence of dyslipidemia in Korean adults is associated with the consumption of amino acids, essential and nonessential types, as well as the sources of these amino acids from food. Methods: Data from 35,478 study participants without dyslipidemia at baseline from the Ansan and Ansung Study and the Health Examinee Study were used for the analysis. Dyslipidemia and its components such as hypertriglyceridemia, hypercholesterolemia, hyper-low-density lipoprotein (LDL) cholesterolemia and hypo-high-density lipoprotein (HDL) cholesterolemia were the main outcome in this study. The participants were categorized into quartiles, based on the intake of amino acids and plant-/animal-based proteins. Results: On average, the follow-up period lasted for 5.7 years. The two major food groups that contributed to one-half of the intake for each type of amino acid were whole grain mixed rice and white rice. Compared to the lowest quartile group, the highest quartile groups of essential amino acid intake [men: hazard ratio (HR) = 0.78; 95% confidence interval (CI), 0.63-0.97; P for trend = 0.0088; women: HR = 0.86; 95% CI, 0.76-0.99; P for trend = 0.0201] and nonessential amino acid intake (men: HR = 0.75; 95% CI, 0.60-0.94; P for trend = 0.0069; women: HR = 0.81; 95% CI, 0.71-0.93; P for trend = 0.0024) had a decreased risk of dyslipidemia. Plant-based protein intake had a negative association and animal-based protein intake had a nonsignificant association with dyslipidemia after adjustment for energy-adjusted fat intake. Furthermore, the essential and nonessential amino acid intake showed stronger negative associations with dyslipidemia after further adjustment for energy-adjusted fat intake. Conclusion: To conclude, the intake of amino acids may have a protective effect against dyslipidemia in Korean adults who are aged 40 years or older, regardless of their protein food sources.

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.

The "fruit and whole-grain" pattern is associated with a low prevalence of hypertriglyceridemia among middle and older-aged Korean adults: Using Korea National Health and Nutrition Examination Survey 2013-2018 data.

Hypertriglyceridemia is a well-known risk factor of various chronic diseases including diabetes mellitus, metabolic syndrome, obesity, and cardiovascular diseases. This study aimed to determine dietary patterns and explore the relationship between dietary patterns and hypertriglyceridemia in the Korean adult population. We utilized a cross-sectional and nationally representative survey, the Korea National Health and Nutrition Examination Survey 2013-2018 database. From 47,217 subjects who participated in the survey between 2013 and 2018, only subjects over 40 years old were included. Subjects lacking 24-h recall data and data on hypertriglyceridemia and body mass index, and who had implausible energy intake were excluded. A total of 19,806 participants' data were analyzed. Dietary data were based on 24-h recall data, and dietary patterns were derived using factor analysis. Triglyceride levels greater than 200 mg/dl were considered hypertriglyceridemia, according to the Korean Society of Lipid and Atherosclerosis. Three dietary patterns- "oil and fats & seasoning", "soybean paste and vegetable", and "fruit and whole-grain"- explained 7.9%, 6.3%, and 5.8% of variation in food intake, respectively. Comparing the lowest and highest dietary pattern score groups after adjusting for potential confounders revealed an inverse relationship between "fruit and whole-grain" dietary pattern and hypertriglyceridemia in men (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.45-0.82, p for trend <.0001); which was only marginal in women (OR: 0.78, 95% CI: 0.58-1.07, p for trend: .628). A diet containing high proportions of fruit and whole-grain may have preventive effects on hypertriglyceridemia in middle and older aged 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.

A review of recent evidence of dietary protein intake and health.

The Korea National Health and Nutrition Examination Survey of 2013 to 2017 reported that the average protein consumption of the Korean population is above the current recommended nutrient intake of protein proposed by the Dietary Reference Intakes for Koreans. Some health professionals and the media often advise consuming diets high in protein for promoting metabolic regulation, weight control, and muscle synthesis. However, due to lack of scientific evidence, the validity and safety of high protein consumption are yet to be fully ascertained. The present review assesses recent evidence published in 2014-2020 from human studies, focusing on adequate protein intake and protein sources for the prevention of chronic diseases, particularly metabolic disorders and sarcopenia.

Effects of Panax ginseng on hyperglycemia, hypertension, and hyperlipidemia: A systematic review and meta-analysis.

Panax ginseng is a medicinal plant is a material with various pharmacological activities and research suggests that it is particularly effective in representative metabolic diseases such as hyperglycemia, hypertension, and hyperlipidemia. Therefore, in this study, systematic review and meta-analysis were performed to investigate the comprehensive effect of P. ginseng on metabolic parameters representing these metabolic diseases. A total of 23 papers were collected for inclusion in the study, from which 27 datasets were collected. The investigational products included P. ginseng and Korean Red ginseng. Across the included studies, the dose ranged from 200 mg to 8 g and the supplementation period lasted from four to 24 weeks. The study subjects varied from healthy adults to those with diabetes, hypertension, obesity, and/or hyperlipidemia. As a result of the analysis, the levels of glucose and insulin area under the curves, % body fat, systolic and diastolic blood pressures, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were significantly reduced in the P. ginseng group as compared with in the placebo group. In conclusion, P. ginseng supplementation may act as an adjuvant to prevent the development of metabolic diseases by improving markers related to blood glucose, blood pressure, and blood lipids.

Barley Sprout Water Extract and Saponarin Mitigate Triacylglycerol Accumulation in 3T3-L1 Adipocytes.

The mechanisms of action responsible for the reported hypolipidemic activity of barley sprouts have yet to be elucidated. The objective of this study was to compare the content of saponarin (the sole flavonoid present in barley sprout leaves), hypolipidemic activity between barley sprout water extract (BSW) and barley sprout ethanol extract (BSE), and the associated relevance to hypolipidemic activity in 3T3-L1 preadipocytes. BSW elicited superior antiadipogenic effects when compared with BSE in MDI mixture [IBMX 0.5 mM + dexamethasone 1 µM + insulin 1 µg/mL]-treated 3T3-L1 preadipocytes. BSW attenuated MDI-mediated triacylglycerol (TAG) accumulation by inhibiting fatty acid synthase (FAS). FAS protein expression was markedly and dose dependently attenuated by BSW, with higher doses suppressing expression to a level equivalent to the controls. BSW also significantly attenuated MDI-mediated increases in the expression of genes involved in TAG synthesis as well as FAS in 3T3-L1 preadipocytes. High-performance liquid chromatography analysis indicated that BSW contains more than four times more saponarin than BSE. Further investigation of saponarin-mediated hypotriacylglycerolemic activity and related gene expression revealed that saponarin significantly inhibited TAG accumulation, which was attributed to reductions in TAG synthesis-related gene expression. Taken together, these findings provide a basis for further development of barley sprout extract for functional health food purposes.

Low Healthy Diet Self-Efficacy and Intentions Associated with High Sweet Snacks and Sugar Sweetened Beverages Consumption among African American Adolescents Recruited from Low-Income Neighborhoods in Baltimore.

Psychosocial factors may influence consumption patterns of sweet snacks and sugar sweetened beverages (SSB), which are potential risk factors for obesity among African American (AA) adolescents. We used multivariable linear and logistic regression models to examine cross-sectional associations among psychosocial factors, sweet snacks and SSB consumption, and BMI z-scores in 437 AA adolescents aged 9-14 years living in low-income neighborhoods in Baltimore City, U.S.A. Mean caloric intake from sugar was 130.64 ± 88.37 kcal. Higher sweet snacks consumption was significantly associated with lower self-efficacy (adjusted Odds Ratio (aOR) = 0.81; 95% CI = 0.71 to 0.93) and lower food intentions scores (0.43; 0.30 to 0.61). Higher SSB consumption was associated with lower outcome expectancies (aOR = 0.98; 95% CI = 0.96-0.99), lower self-efficacy (0.98; 0.96 to 0.99), and lower food intentions (0.91; 0.87 to 0.95). No significant association was found between SSB and sweet snacks consumption and weight status. Psychosocial factors may play a role in sugar consumption behaviors among AA adolescents in low-income neighborhoods. Further studies are needed to improve our understanding of causal mechanisms of this association.

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.

Association of Coffee Consumption and Its Types According to Addition of Sugar and Creamer with Metabolic Syndrome Incidence in a Korean Population from the Health Examinees (HEXA) Study.

Coffee is widely consumed worldwide, and numerous studies indicate that coffee consumption may potentially affect the development of chronic diseases. Metabolic syndrome (MetS) may constitute a risk factor for chronic diseases. We aimed to prospectively evaluate the association between coffee consumption and MetS incidence. All participants were selected from the Health Examinees study. MetS was defined by the Adult Treatment Panel III criteria of the National Cholesterol Education Program. A multivariate Cox proportional hazards regression model was used to assess the relationship between coffee consumption and MetS incidence. In comparison with non-consumers, male moderate consumers (≤3 cups/day) showed a lower risk for low high-density lipoprotein cholesterol (HDL-C) (≤1 cup/day, hazard ratio (HR): 0.445, 95% confidence interval (CI): 0.254-0.780; 1-3 cups/day, HR: 0.507, 95% CI: 0.299-0.859) and high fasting blood glucose (FPG) (≤1 cup/day, HR: 0.694, 95% CI: 0.538-0.895; 1-3 cups/day, HR: 0.763, 95% CI: 0.598-0.972). Male 3-in-1 coffee (coffee with sugar and creamer) consumers also showed a lower risk for low HDL-C (HR: 0.423, 95% CI: 0.218-0.824) and high FPG (HR: 0.659, 95% CI: 0.497-0.874). These findings indicate a negative association between moderate coffee consumption and low HDL-C and high FPG among Korean male adults.

Comparative study of the effects of diosmin and diosmetin on fat accumulation, dyslipidemia, and glucose intolerance in mice fed a high-fat high-sucrose diet.

This study compared the effects of diosmin and its aglycone, diosmetin, on body weight, liver fat, serum cholesterol, and glucose intolerance in male C57BL/6 mice fed a high-fat high-sucrose (HFHS) diet for 12 weeks. The mice were divided into four groups that received the following diets: normal diet (ND), HFHS diet, HFHS diet with 0.5% diosmin, and HFHS diet with 0.5% diosmetin. The body weight increased significantly in the HFHS diet group but decreased significantly in the HFHS diet with 0.5% diosmin group. The diosmin and diosmetin treatment inhibited fat accumulation in liver and epididymal tissues, and improved glucose intolerance by lowering glucose levels during a glucose tolerance test; these effects were greater in the diosmin group than those in the diosmetin group. Furthermore, only diosmin significantly ameliorated dyslipidemia, by reducing TC and LDL-C levels, while diosmetin had little effect on these parameters. Taken together, the results showed that diosmin and diosmetin can prevent fat accumulation and glucose intolerance; however, diosmin was more effective and also showed an antidyslipidemic effect.

Animal Protein Intake Is Positively Associated with Metabolic Syndrome Risk Factors in Middle-Aged Korean Men.

Few studies have examined the relationship of protein intake by food source with metabolic syndrome in Korean adults, even though animal food intake has increased. This study examined the association between plant and animal protein intake and metabolic syndrome among middle-aged Korean adults. A total of 13,485 subjects aged 30-64 years were selected from the 2013-2018 Korea National Health and Nutrition Examination Survey. Protein intake was assessed using 24-h dietary recall data and divided into quintiles. Men had a higher percentage of energy intake from animal protein (7.4%) than plant protein (6.9%). Men in the highest quintile group of animal protein intake had a higher prevalence of abdominal obesity (OR: 1.30, 95% CI: 1.00-1.70), reduced high-density lipoprotein cholesterol (HDL-C) (OR: 1.43, 95% CI: 1.07-1.90), and elevated fasting glucose (OR: 1.32, 95% CI: 1.01-1.74), after adjusting for covariates. Furthermore, stronger associations of animal protein intake with abdominal obesity were shown in men who consumed less than estimated energy requirements (OR: 1.60, 95% CI: 1.11-2.31). Plant protein intake was negatively associated with increased blood pressure in men. Neither animal nor plant protein intakes were significantly associated with any of the metabolic syndrome risk factors in women. The results imply that lower animal protein intake may be a beneficial factor for metabolic syndrome management in middle-aged Korean men.

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.

Anacardic acid mitigates liver fat accumulation and impaired glucose tolerance in mice fed a high-fat and high-sucrose diet.

In this study, we evaluated the effects of anacardic acid (AA), a phenolic lipid found in cashew nuts (Anacardium occidentale), on metabolic disorders related to obesity, fatty liver disease, and diabetes using both in vitro and in vivo models. The application of AA led to a reduction in lipid accumulation in 3T3-L1 cells without observable cytotoxicity. Results from Western blot analysis revealed that AA treatment also led to decreased expression of fatty acid synthase and peroxisome proliferator-activated receptor gamma. In vivo studies were performed to evaluate the effects of AA treatment on fatty liver disease and diabetes. Mice fed a high-fat and high-sucrose diet had significantly higher body and liver weights, and higher levels of liver fat, cholesterol, fasting glucose, and homeostasis model assessment of insulin resistance (HOMA-IR). However, 12 weeks of oral treatment with 500 µg/kg BW AA slowed down lipid accumulation rates in the liver and mitigated insulin resistance in these mice. Thus, AA may reduce lipid levels and have an antidiabetic effect.

Fat Intake and Stress Modify Sleep Duration Effects on Abdominal Obesity.

Though the association between sleep duration and obesity has been generally acknowledged, there is little information about the mechanisms behind this association. The purpose of this study was to examine the effect of the fat intake and stress variables on the association between sleep duration and abdominal obesity. Data for 13,686 subjects aged ≥ 20 years from the 2013-2017 Korea National Health and Nutrition Examination Survey were used, and hierarchical and stratified logistic regression analyses were employed. In the hierarchical logistic regression analyses, fat intake and stress did not change the significance or the size of the sleep effects upon abdominal obesity. These results suggest that sleep duration does not affect abdominal obesity through fat intake or stress variables. In addition, fat intake and stress are not mediators of the sleep duration variable. However, subjects with different levels of fat intake and stress showed different associations between sleep duration and abdominal obesity. Subjects who were in the lowest or highest group of fat intake as well as self-reported stress level showed a weaker relationship between sleep duration and abdominal obesity, compared with the other groups. In conclusion, fat intake and stress modify the effects of sleep duration on abdominal obesity according to the stratified regression results.

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.

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.

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.

Free fatty acid-induced histone acetyltransferase activity accelerates lipid accumulation in HepG2 cells.

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including PPARγ, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.