Association of Dietary Resistant Starch Intake with Obesity and Metabolic Syndrome in Korean Adults.

Research findings on the relationship between dietary resistant starch (RS) intake and metabolic diseases using population-based data are very scarce. This study examined the association of dietary RS intake with obesity and metabolic syndrome in Korean adults. A total of 12,491 adults (5292 men and 7199 women) were selected from the 2016-2018 Korea National Health and Nutrition Examination Survey data. The individual RS intake (g) was calculated by linking the 1-day 24 h recall data with the RS content database for common Korean foods. Obesity was defined as a BMI ≥ 25.0 kg/m2. Metabolic syndrome was defined as having three or more of the following: abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated fasting blood glucose, and elevated blood pressure. Odds ratios (ORs) with 95% confidence intervals (CIs) for obesity and metabolic syndrome across quartiles (Qs) of RS intake were calculated using multiple logistic regression analysis. In men, the highest quartile of RS intake showed a significantly lower OR for metabolic syndrome compared to the lowest quartile after adjusting for covariates (OR = 0.71, 95% CI = 0.56-0.92, p-trend = 0.0057). Dietary RS intake in men was also inversely associated with obesity (Q4 vs. Q1: OR = 0.80, 95% CI = 0.67-0.97, p-trend = 0.0329) and elevated triglycerides (Q4 vs. Q1: OR = 0.80, 95% CI = 0.66-0.98, p-trend = 0.0314). In women, RS intake was not associated with metabolic syndrome. Our findings may serve as useful data for developing guidelines for RS intake and conducting further cohort and clinical studies to investigate the health effects of RS.

Prospective Associations between Dietary Patterns and Abdominal Obesity in Middle-Aged and Older Korean Adults.

This study aimed to identify major dietary patterns associated with abdominal obesity in middle-aged and older Korean adults. Data from the Korean Genome and Epidemiology Study were used. A total of 48,037 Korean adults aged ≥40 years without abdominal obesity at baseline were followed-up. Dietary assessment was conducted using a validated 106-item food-frequency questionnaire, and dietary patterns were identified using factor analysis. Abdominal obesity was defined as a waist circumference of ≥90 cm for men and ≥85 cm for women, according to the Korean Society for the Study of Obesity. Multivariable Cox proportional-hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the future risk of abdominal obesity for each dietary pattern after adjusting for potential covariates. After an average follow-up of 4.89 years, we reported 5878 cases (1932 men and 3946 women) of abdominal obesity. Based on factor analysis, three major dietary patterns were identified in both men and women: the "healthy", "coffee and sweets", and "multi-grain" patterns. In the fully adjusted model, the "healthy" pattern was inversely associated with the incidence of abdominal obesity (HR for fourth vs. first quartile: 0.86; 95% CI: 0.75-0.98; p for trend = 0.0358 for men; HR for fourth vs. first quartile: 0.90; 95% CI: 0.83-0.99; p for trend = 0.0188 for women), whereas the "coffee and sweets" pattern was positively associated with it (HR for fourth vs. first quartile: 1.23; 95% CI: 1.08-1.40; p for trend = 0.0495 for men; HR for fourth vs. first quartile: 1.14; 95% CI: 1.04-1.25; p for trend = 0.0096 for women). In contrast, the "multi-grain" pattern in men and women showed no significant association with the incidence of abdominal obesity. Diets rich in colorful vegetables, seaweeds, mushrooms, tubers, fruits, soy products, and fish and low in coffee, sweets, and oils/fats might be favorable for reducing the future risk of abdominal obesity, particularly in middle-aged and older Korean adults.

Identifying the Associations of Nightly Fasting Duration and Meal Timing with Type 2 Diabetes Mellitus Using Data from the 2016-2020 Korea National Health and Nutrition Survey.

Nightly fasting duration and meal timing are associated with metabolic disorders. This study aimed to investigate the relationships of nightly fasting duration and meal timing with type 2 diabetes mellitus (T2DM) using data from the 2016-2020 Korea National Health and Nutrition Survey. A total of 22,685 adults ≥ 19 years were included in this study. Nightly fasting duration was calculated by subtracting the interval between the day's first and last meal eating times from 24 h. The meal timing were analyzed using various parameters, including the times of the first and last eating episodes and the percentage of energy intake during the morning (05:00 to 9:00 a.m.), evening (06:00 to 09:00 p.m.), and night (after 09:00 p.m.). Men who fasted nightly for ≥ 12 h had lower odds of T2DM (odds ratio (OR): 0.86; 95% confidence interval (CI): 0.75-0.99) than those who fasted for < 12 h. Individuals who had their last meal after 09:00 p.m. had higher odds of T2DM (OR: 1.19, 95% CI: 1.03-1.38, men; OR: 1.19, 95% CI: 1.01-1.40, women). Additionally, the percentage of energy intake during the evening was associated with increased odds of T2DM (OR: 1.41, 95% CI: 1.08-1.84, men; OR: 1.32, 95% CI: 1.02-1.70, women). These findings emphasize the importance of nightly fasting duration and meal timing in modulating the risk of T2DM among Korean adults.

Anti-Obesity Effects of Petasites japonicus (Meowi) Ethanol Extract on RAW 264.7 Macrophages and 3T3-L1 Adipocytes and Its Characterization of Polyphenolic Compounds.

Koreans have been consuming Petasites Japonicus (PJ) as food. Although the therapeutic effect of PJ on allergic or inflammatory reactions associated with asthma has been proven, its effect on obesity is unclear. Therefore, the present study was aimed to assess the obesity related anti-inflammatory and anti-adipogenic effects of ethanol extract PJ (EPJ) on the inflammatory response in RAW 264.7 macrophages and on differentiation in 3T3-L1 adipocytes. In addition, the polyphenolic compound was quantitatively characterized from the EPJ using ultra performance liquid chromatography coupled with diode array detector, quadrupole time-of-flight-mass spectrometry (UPLC-DAD-QToF-MS). In RAW 264.7 or 3T3-L1, reduction of nitric oxide (in macrophages) production as well as monocyte chemoattractant protein-1 and tumor necrosis factor-α were observed. Treatment of EPJ in adipocyte differentiation showed an improvement in adiponectin and lipid accumulation and a significant reduction of PPARγ and FABP-4 mRNA expression levels. On the other hand, mRNA expression of UCP-1, PPARα, and ACO increased in the EPJ treated group. In addition, a total of 26 polyphenolic compounds were detected and of which 12 are reported for the first time from PJ. The higher content of diverse polyphenolic compounds presented in EPJ might be responsible for the observed anti-inflammatory and anti-adipogenic effect. These results suggest that PJ is valuable in improving obesity-related inflammatory responses.

Effect of a balanced Korean diet on metabolic risk factors among overweight/obese Korean adults: a randomized controlled trial.

PURPOSE: This study was to see the effects of a balanced Korean diet (BKD) on metabolic risk factors in overweight or obese Korean adults, comparing with those of a typical American diet (TAD) and a diet recommended by the 2010 Dietary Guidelines for Americans (2010DGA). METHODS: The study was designed as a randomized crossover controlled trial, in which 61 overweight or obese volunteers were divided into six groups and each consumed the BKD, 2010DGA, and TAD in a random order for 4 weeks separated by 2-week washout intervals. Anthropometric indices, blood pressure, blood lipid content, fasting blood glucose, and blood insulin level were measured at the beginning and end of each diet period. RESULTS: A total of 54 participants completed the trial. The BKD caused more significant reductions of body mass index (BMI) (p < 0.001), body fat percent (p < 0.001), blood total cholesterol (p < 0.001), and low-density lipoprotein (LDL) cholesterol (p = 0.007) compared with the 2010DGA or TAD (all p values for differences between diets < 0.05). All three diets significantly lowered blood triglyceride levels (p < 0.05). The BKD decreased high-density lipoprotein (HDL) cholesterol (p = 0.001) and increased fasting blood glucose (p = 0.018), whereas TAD and 2010DGA increased HDL cholesterol and did not affect blood glucose levels. Furthermore, the BKD significantly decreased the proportion of individuals with elevated total cholesterol (p < 0.001) and LDL cholesterol (p < 0.01), whereas the 2010DGA significantly reduced the number of obese individuals (p < 0.05), and the TAD decreased the number of participants with elevated triglyceride levels (p < 0.05), but increased that of those with elevated LDL cholesterol (p < 0.05). CONCLUSIONS: The Korean diet based on dietary guidelines improved metabolic risk factors such as BMI, body fat percent, and blood lipid profiles in overweight or obese Korean adults. These results provide evidence to recommend the Korean diet for preventing various metabolic diseases. CLINICAL TRIAL REGISTRATION: The trial was registered at the Clinical Research Information Service (CRIS) in Korea, the primary registry of the World Health Organization (WHO) international clinical trial registry platform, under number KCT0002437.

Differential Effects of Typical Korean Versus American-Style Diets on Gut Microbial Composition and Metabolic Profile in Healthy Overweight Koreans: A Randomized Crossover Trial.

The Westernized diet has been associated with the pathogenesis of metabolic diseases, whereas a Korean diet has been reported to exert beneficial effects on health in several studies. However, the effects of Western and Korean diets on the gut microbiome and host metabolome are unclear. To examine the diet-specific effects on microbiome and metabolome, we conducted a randomized crossover clinical trial of typical Korean diet (TKD), typical American diet (TAD), and recommended American diet (RAD). The trial involved a 4-week consumption of an experimental diet followed by a 2-week interval before diet crossover. 16S rRNA sequencing analysis identified 16, 10, and 14 differential bacteria genera specific to TKD, RAD, and TAD, respectively. The Firmucutes-Bacteroidetes ratio was increased by TKD. Nuclear magnetic resonance metabolome profiling revealed that TKD enriched branched chain amino acid metabolism, whereas ketone body metabolism was evident in RAD and TAD. Microbiome and metabolome responses to the experimental diets varied with individual enterotypes. These findings provide evidence that the gut microbiome and host metabolome rapidly respond to different cultural diets. The findings will inform clarification of the diet-related communication networks of the gut microbiome and host metabolome in humans.

A randomized trial on the effects of 2010 Dietary Guidelines for Americans and Korean diet patterns on cardiovascular risk factors in overweight and obese adults.

BACKGROUND: Dietary patterns that are considered healthy (eg, the Dietary Approaches to Stop Hypertension diet and Mediterranean diet) may be more successful in reducing typical cardiovascular disease risks compared to dietary patterns considered unhealthy (eg, energy-dense diets such as the typical American diet). OBJECTIVE: This study assessed the effects of a Korean diet, the 2010 Dietary Guidelines for Americans (DGA), and a typical American diet on cardiometabolic risk factors, including lipid levels and blood pressure, in overweight, non-Asian individuals in the United States with elevated low-density lipoprotein cholesterol. DESIGN/INTERVENTION: The study was a three-period crossover, controlled-feeding study from January 2012 to May 2012. Thirty-one subjects were randomly allocated to one of six possible sequential orders for consuming the three diets for 4 weeks, each separated by a 10-day break. Data analysis included 27 subjects on the Korean diet periods and 29 in the DGA and typical American diet periods. Subjects remained weight stable. MAIN OUTCOME MEASURES: Lipid profile, blood pressure, insulin, glucose, and 24-hour urinary sodium were determined at baseline and at the end of each diet period. STATISTICAL ANALYSES PERFORMED: The additive main effects multiplicative interactions model was used to test for a subject by diet interaction. Differences among diets were determined using a mixed-models procedure (PROC MIXED) with random intercept for each subject. RESULTS: Total cholesterol and low-density lipoprotein cholesterol significantly decreased on Korean (P<0.0001 and P<0.01, respectively) and DGA (P<0.01 and P<0.05, respectively) diets, but not on the typical American diet. Although an unfavorable outcome, high-density lipoprotein cholesterol significantly decreased on all three diets (Korean: P<0.0001; DGA: P<0.0001; typical American: P<0.05). No diet had a significant effect on serum triglycerides, but a slight increase in triglycerides in the Korean and decrease in the DGA resulted in a significant difference between these two diets (P<0.01). All three diets caused modest decreases in systolic and diastolic blood pressure, which reached statistical significance for DGA only (P<0.05 and P<0.01, respectively). No diet had significant effect on fasting insulin, whereas fasting glucose decreased significantly on the Korean (P<0.01) and typical American (P<0.05) diets only. Urinary sodium output decreased significantly on DGA (P<0.0001). CONCLUSIONS: After a 4-week feeding period, Korean and DGA diet patterns resulted in positive changes in cardiovascular disease risk factors.

Effect of coenzyme Q10 and Ardisia japonica Blume on plasma and liver lipids, platelet aggregation, and erythrocyte Na efflux channels in simvastatin-treated guinea pigs.

Forty guinea pigs were divided into four groups and fed 0.04% cholesterol based control diet, plus 0.05% simvastatin, and statin plus 0.1% CoQ10 or 10% Ardisia Japonica Blume (AJB) leave powder for 4 weeks. Plasma total cholesterol levels decreased significantly in all groups fed the statin-containing diet compared with that in guinea pigs fed the control diet (P < 0.01). Plasma and liver triglycerides decreased significantly in the statin plus CoQ10 group compared with those in the control (both P < 0.05). Maximum platelet aggregation was significantly higher in the statin plus CoQ10 group than that in the other groups (P < 0.05). Na-K ATPase activity increased in the statin group and decreased in the statin plus CoQ10 group (P < 0.01). Na-K co-transport and Na passive transport decreased significantly in the control group compared with those in the other groups (both P < 0.05). Intracellular Na was highest in the statin group and lowest in the statin plus CoQ10 group and was correlated with Na-K ATPase activity. Thiobarbituric acid reactive substance production in platelet-rich plasma and liver tended to decrease in the statin plus CoQ10 group compared with those in the other groups. Plasma glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase increased significantly in the statin group compared with those in the control (P < 0.05). These result suggest that antioxidant rich AJB did not have positive effects on cardiovascular disease parameters. The statin plus CoQ10 seemed to decrease cholesterol more efficiently than that of statin alone.

Bixin activates PPARα and improves obesity-induced abnormalities of carbohydrate and lipid metabolism in mice.

Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates the expression of the genes involved in fatty acid oxidation. PPARα activators induce fatty acid oxidation in the liver, thereby improving lipid and carbohydrate metabolism in obese mice. In this study, the dietary cis-carotenoids bixin and norbixin, which are commonly used in the food coloring industry, were found to activate PPARα by luciferase reporter assays using GAL4/PPARα chimeric and full-length PPARα systems. Treatment with bixin and norbixin induced the mRNA expression of PPARα target genes involved in fatty acid oxidation in PPARα-expressing HepG2 hepatocytes. In obese KK-Ay mice, bixin treatment suppressed the development of hyperlipidemia and hepatic lipid accumulation. In the livers of bixin-treated mice, the mRNA levels of PPARα target genes related to fatty acid oxidation were up-regulated. Moreover, bixin treatment also improved obesity-induced dysfunctions of carbohydrate metabolism, such as hyperglycemia, hyperinsulinemia, and hypoadiponectinemia. Glucose tolerance test and insulin tolerance test revealed that glucose intolerance and insulin resistance in KK-Ay obese mice were attenuated by the treatment with bixin. These results indicate that bixin acts as a food-derived agonist of PPARα, and bixin treatment is useful for the management of obesity-induced metabolic dysfunctions in mice.

Effects of green tea or Sasa quelpaertensis bamboo leaves on plasma and liver lipids, erythrocyte Na efflux, and platelet aggregation in ovariectomized rats.

This study was conducted to investigate the effects of Sasa quelpaertensis bamboo and green tea on plasma and liver lipids, platelet aggregation, and erythrocyte membrane Na channels in ovariectomized (OVX) rats. Thirty female rats were OVX, and ten female rats were sham-operated at the age of 6 weeks. The rats were divided into four groups at the age of 10 weeks and fed the experiment diets: sham-control, OVX-control, OVX-bamboo leaves (10%), or OVX-green tea leaves (10%) for four weeks. Final body weight increased significantly in the OVX groups compared with that in the sham-control, whereas body weight in the OVX-green tea group decreased significantly compared with that in the OVX-control (P < 0.01). High density lipoprotein (HDL)-cholesterol level decreased in all OVX groups compared with that in the sham-control rats (P < 0.05) but without a difference in plasma total cholesterol. Plasma triglycerides in the OVX-green tea group were significantly lower than those in the sham-control or OVX-control group (P < 0.05). Liver triglycerides increased significantly in the OVX-control compared with those in the sham-control (P < 0.01) but decreased significantly in the OVX-green tea group compared with those in the OVX-control or OVX-bamboo group (P < 0.01). Platelet aggregation in both maximum and initial slope tended to be lower in all OVX rats compared with that in the sham-control rats but was not significantly different. Na-K ATPase tended to increase and Na-K cotransport tended to decrease following ovariectomy. Na-K ATPase decreased significantly in the OVX-green tea group compared with that in the OVX-control group (P < 0.01), and Na-K cotransport increased significantly in the OVX-bamboo and OVX-green tea groups compared with that in the OVX-control (P < 0.05). Femoral bone mineral density tended to be lower in OVX rats than that in the sham-control, whereas the green tea and bamboo leaves groups recovered bone density to some extent. The results show that ovariectomy caused an increase in body weight and liver triglycerides, and that green tea was effective for lowering body weight and triglycerides in OVX rats. Ovariectomy induced an increase in Na efflux via Na-K ATPase and a decrease in Na efflux via Na-K cotransport. Furthermore, consumption of green tea and bamboo leaves affected Na efflux channels, controlling electrolyte and body water balance.

Dehydroabietic acid activates peroxisome proliferator-activated receptor-γ and stimulates insulin-dependent glucose uptake into 3T3-L1 adipocytes.

Dehydroabietic acid (DAA) is a food-derived terpenoid with various bioactivities. Our previous study has revealed that DAA activates peroxisome proliferator-activated receptor-γ (PPARγ) in luciferase assay and suppresses chronic inflammation in obese adipose tissues. In this study, we examined the effects of DAA on adipocyte differentiation. DAA treatment stimulated the adipocyte differentiation of 3T3-L1 preadipocytes. The DAA treatment increased the mRNA expression levels of adipocyte differentiation marker genes such as aP2, lipoprotein lipase (LPL), and PPARγ. In particular, the expression level of adiponectin, which is an adipocytokine with stimulatory effects on insulin sensitivity, was increased at both the mRNA and protein levels by the DAA treatment. Moreover, the DAA treatment stimulated insulin-dependent glucose uptake into differentiated 3T3-L1 adipocytes. These findings indicate that DAA stimulates adipocyte differentiation and insulin sensitivity in 3T3-L1 cells, suggesting that DAA is a valuable food-derived compound for the management of metabolic syndrome.

Diosgenin, the main aglycon of fenugreek, inhibits LXRα activity in HepG2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice.

Trigonella foenum-graecum (fenugreek) can ameliorate dyslipidemia, but the detailed mechanism is unclear. In this study, we examined the effects of fenugreek on hepatic lipid metabolism, particularly lipogenesis, which is enhanced in obesity and diabetes, in diabetic obese KK-Ay mice. KK-Ay mice were fed a control high-fat diet (HFD; 60% of energy as fat) (C group) or an HFD containing 0.5% or 2% fenugreek (0.5F and 2.0F groups, respectively) for 4 wk. Hepatic and plasma TG and mRNA expression levels of lipogenic genes were lower in the 2.0F group at 4 wk (P < 0.05), but not in the 0.5F group, than in the C group. The hydrolyzed saponin fraction, but not the saponin fraction per se, in fenugreek inhibited the accumulation of TG in HepG2 cells. We fractionated the hydrolyzed saponin into 15 fractions by HPLC and examined the effect of these fractions on TG accumulation in HepG2 cells. Fraction 11 inhibited TG accumulation in HepG2 cells and we determined by liquid chromatography tandem MS that the active substance contained in fraction 11 is diosgenin. Diosgenin (5 and 10 µmol/L) inhibited the accumulation of TG and the expression of lipogenic genes in HepG2 cells. Moreover, diosgenin inhibited the transactivation of liver-X-receptor-α, as measured using a luciferase assay system and by gel mobility shift assay. These findings suggest that fenugreek ameliorates dyslipidemia by decreasing the hepatic lipid content in diabetic mice and that its effect is mediated by diosgenin. Fenugreek, which contains diosgenin, may be useful for the management of diabetes-related hepatic dyslipidemias.

Dehydroabietic acid, a diterpene, improves diabetes and hyperlipidemia in obese diabetic KK-Ay mice.

Terpenoids, which are contained in a large number of dietary and herbal plants, have many biological effects. In this study, the effects of dehydroabietic acid (DAA), a diterpene, on glucose and lipid metabolism were examined using obese diabetic KK-Ay mice. We showed here that DAA treatment decreased not only plasma glucose and insulin levels but also plasma triglyceride (TG) and hepatic TG levels. To examine the mechanism underlying the effects of DAA, the production of inflammatory cytokines was measured. It was shown that the DAA treatment suppressed the production of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNFalpha) (proinflammatory cytokines) and increased that of adiponectin (an anti-inflammatory cytokine). As a result of the changes in the production of inflammatory cytokines caused by the DAA treatment, the accumulation of macrophages in adipose tissues was reduced. These results indicate that treatment with DAA improves the levels of plasma glucose, plasma insulin, plasma TG, and hepatic TG through the decrease in the macrophage infiltration into adipose tissues, suggesting that DAA is a useful food-derived compound for treating obesity-related diseases.

6-Shogaol and 6-gingerol, the pungent of ginger, inhibit TNF-alpha mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes.

In this study, we demonstrated that the two ginger-derived components have a potent and unique pharmacological function in 3T3-L1 adipocytes via different mechanisms. Both pretreatment of 6-shogaol (6S) and 6-gingerol (6G) significantly inhibited the tumor necrosis factor-alpha (TNF-alpha) mediated downregulation of the adiponectin expression in 3T3-L1 adipocytes. Our study demonstrate that (1) 6S functions as a PPARgamma agonist with its inhibitory mechanism due to the PPARgamma transactivation, and (2) 6G is not a PPARgamma agonist, but it is an effective inhibitor of TNF-alpha induced c-Jun-NH(2)-terminal kinase signaling activation and thus, its inhibitory mechanism is due to this inhibitory effect.

Dietary regulation of nuclear receptors in obesity-related metabolic syndrome.

In Western culture, excess visceral fat accumulation or obesity has reached epidemic proportions, resulting in metabolic syndrome. However, more than 10 years of research has shown that adipocytes also function as endocrine cells that release various bioactive substances, so called "adipocytokines or adipokines", that play a major role in the regulation of food intake, insulin sensitivity, energy metabolism, and the vascular microenvironment. Adiponectin, an adipocytokine, is considered to improve insulin sensitivity. Recently, monocyte chemoattractant protein (MCP)-1 has been reported to be a novel adipocytokine involved in the development of obesity-associated insulin resistance and atherosclerosis. Nuclear receptors, especially peroxisome proliferator-activated receptor-alpha (PPAR alpha) and PPAR gamma are ligand-activated transcription factors that regulate the metabolism of glucose and lipids. PPAR gamma is strongly expressed in adipocytes and plays a significant role in the transcriptional activation of adipocytokines including adiponectin. PPAR alpha, another PPAR isoform, is involved in the control of lipid metabolism in the liver and skeletal muscle. PPAR alpha activation causes lipid clearance via beta-oxidation enhancement. We showed that various dietary terpenoids and other natural ingredients regulate the transcription of PPAR target genes, induces the expression and secretion of adiponectin, and inhibits those of MCP-1 in adipocytes and beta-oxidation in liver. These findings indicate that dietary factor acts as an agonist of PPARs and is a valuable medical and food component for the gradual improvement of metabolic syndrome.

Dehydroabietic acid, a phytochemical, acts as ligand for PPARs in macrophages and adipocytes to regulate inflammation.

Obesity is characterized by an enhanced infiltration of macrophages to adipose tissues, which is closely associated with the low-grade inflammatory state and obesity-related pathologies such as type 2 diabetes and cardiovascular diseases. We showed here that dehydroabietic acid (DAA) is a potent PPARalpha/gamma dual activator. Furthermore, we examined the anti-inflammatory effects of DAA in stimulated macrophages and in the coculture of macrophages and adipocytes. DAA significantly suppressed the production of proinflammatory mediators such as MCP-1, TNF-alpha, and NO in stimulated RAW 264 macrophages and in the coculture of RAW 264 macrophages and 3T3-L1 adipocytes. These results suggest that DAA is a valuable medicinal and food component for improving inflammatory changes associated with obesity-related diabetes.

Auraptene, a citrus fruit compound, regulates gene expression as a PPARalpha agonist in HepG2 hepatocytes.

Citrus fruit compounds have various activities that improve pathological conditions in many tissues. In this study, we examined the effect of auraptene contained mainly in the peel of citrus on peroxisome proliferator-activated receptor-alpha (PPARalpha) activation. To examine effects of auraptene on the PPARalpha activation in hepatocytes, PPAR ligand assay system was developed using HepG2 hepatocytes, in which the endogenous PPARalpha expression level is very low. In the PPAR ligand assay, the addition of auraptene showed significant effects on the transactivation of GAL4/PPARalpha chimera proteins in a dose-dependent manner. Actually, treatment with auraptene induced the up-regulation of PPAR target genes, such as acyl-CoA oxidase (ACO), carnitine-palmitoyl transferase 1A (CPT1A) and acyl-CoA synthetase (ACS), in PPARalpha-expressing HepG2 hepatocytes. The regulation of gene expression was dependent on PPARalpha because mock-transfected HepG2 hepatocytes showed no regulation. The up-regulation of PPAR target gene expression by auraptene was sufficient to enhance oleic acid uptake into PPARalpha-expressing HepG2 hepatocytes. These results indicate that auraptene acts as a PPARalpha agonist in hepatocytes and that auraptene may improve lipid abnormality through PPARalpha activation in the liver.

Citrus auraptene acts as an agonist for PPARs and enhances adiponectin production and MCP-1 reduction in 3T3-L1 adipocytes.

Citrus fruit compounds have many health-enhancing effects. In this study, using a luciferase ligand assay system, we showed that citrus auraptene activates peroxisome proliferator-activated receptor (PPAR)-alpha and PPARgamma. Auraptene induced up-regulation of adiponectin expression and increased the ratio of the amount of high-molecular-weight multimers of adiponectin to the total adiponectin. In contrast, auraptene suppressed monocyte chemoattractant protein (MCP)-1 expression in 3T3-L1 adipocytes. Experiments using PPARgamma antagonist demonstrated that these effects on regulation of adiponectin and MCP-1 expression were caused by PPARgamma activations. The results indicate that auraptene activates PPARgamma in adipocytes to control adipocytekines such as adiponectin and MCP-1 and suggest that the consumption of citrus fruits, which contain auraptene can lead to a partial prevention of lipid and glucose metabolism abnormalities.

Inhibitory effect of naringenin chalcone on inflammatory changes in the interaction between adipocytes and macrophages.

Obese adipose tissue is characterized by an enhanced infiltration of macrophages. It is considered that the paracrine loop involving monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha between adipocytes and macrophages establishes a vicious cycle that augments the inflammatory changes and insulin resistance in obese adipose tissue. Polyphenols, which are widely distributed in fruit and vegetables, can act as antioxidants and some of them are also reported to have anti-inflammatory properties. Tomato is one of the most popular and extensively consumed vegetable crops worldwide, which also contains many flavonoids, mainly naringenin chalcone. We investigated the effect of flavonoids, including naringenin chalcone, on the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages and in the interaction between adipocytes and macrophages. Naringenin chalcone inhibited the production of TNF-alpha, MCP-1, and nitric oxide (NO) by LPS-stimulated RAW 264 macrophages in a dose-dependent manner. Coculture of 3T3-L1 adipocytes and RAW 264 macrophages markedly enhanced the production of TNF-alpha, MCP-1, and NO compared with the control cultures; however, treatment with naringenin chalcone dose-dependently inhibited the production of these proinflammatory mediators. These results indicate that naringenin chalcone exhibits anti-inflammatory properties by inhibiting the production of proinflammatory cytokines in the interaction between adipocytes and macrophages. Naringenin chalcone may be useful for ameliorating the inflammatory changes in obese adipose tissue.

cDNA cloning of halocidin and a new antimicrobial peptide derived from the N-terminus of Ci-META4.

Halocidin is an antimicrobial peptide, which is isolated from hemocytes from the tunicate, Halocynthiaaurantium. In this study, we cloned the full-length cDNA of halocidin from pharyngeal tissue, using a combination of RT-PCR and 5'-RACE-PCR. The observed cDNA structure indicated that halocidin is synthesized as a 10.37 kDa prepropeptide. Based on the cDNA structure and the known amino acid sequence of the mature peptide, it was concluded that the precursor of halocidin contains a 21-residue signal peptide, followed by the 18 residues of the mature peptide, and a 56-residue anionic C-terminal extension, which is removed later on in the process. The signal sequence of halocidin exhibited a high degree of similarity with the corresponding portion of the Ci-META4 protein, which had been previously discovered in the coelomic cells of another tunicate, Cionaintestinalis, and is considered to play a role in metamorphosis. However, in several respects, the cDNA structure of Ci-META4 suggested that it might constitute a precursor for an antimicrobial peptide. Thus, we prepared a synthetic peptide, which was comprised of 19 N-terminal amino acid residues in the predicted mature region of Ci-META4, and tested it with regard to its antimicrobial activity. As a result, we confirmed that the synthetic peptide exhibited potent antimicrobial activity against Gram (+) and (-) bacteria, while evidencing no hemolytic activity toward human erythrocytes.