Green Tea Extracts Attenuate Brain Dysfunction in High-Fat-Diet-Fed SAMP8 Mice.

Unhealthy diet promotes progression of metabolic disorders and brain dysfunction with aging. Green tea extracts (GTEs) have various beneficial effects and alleviate metabolic disorders. GTEs have neuroprotective effects in rodent models, but their effects against brain dysfunction in models of aging fed unhealthy diets are still unclear. Here, we showed that GTEs attenuate high-fat (HF) diet-induced brain dysfunction in senescence-accelerated mouse prone-8 (SAMP8), a murine model of senescence. SAMP8 mice were fed a control diet, HF diet, or HF diet with 0.5% GTEs (HFGT) for four months. The HF diet reduced memory retention and induced amyloid ß1-42 accumulation, whereas GTEs attenuated these changes. In HF diet-fed mice, lipid oxidative stress, assessed by malondialdehyde levels, was increased. The levels of proteins that promote synaptic plasticity, such as brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95), were reduced. These alterations related to brain dysfunction were not observed in HFGT diet-fed mice. Overall, our data suggest that GTEs intake might attenuate brain dysfunction in HF diet-fed SAMP8 mice by protecting synaptic plasticity as well as via anti-oxidative effects. In conclusion, GTEs might ameliorate unhealthy diet-induced brain dysfunction that develops with aging.

Effects of promoting daily physical activity on physical and mental health in older individuals.

[Purpose] A trial was conducted to examine the effects of promoting daily physical activity, tailored to specific living situations, on physical and mental health indicators in older adults. [Participants and Methods] Participants in the 'Intervention' group (N=21) wore accelerometers during the 12-week trial period, and for one week during preliminary and follow-up surveys. Based on their physical activity levels as measured by accelerometers, participants were given instructions to increase their daily physical activity. Participants in the 'Control' group (N=18) wore the accelerometer only during the preliminary and follow-up survey. [Results] Number of steps increased significantly in the intervention group and a significant decrease in light physical activity time was observed in the control group. No such decrease was observed in the intervention group. With regard to health-related quality of life, significant interactions were observed between groups based on the 36-Item Short-Form Health Survey Mental Component Summary score, and some sub-items. A combined analysis of both groups found a significant positive correlation between the change in light physical activity time and the Mental Component Summary score. [Conclusion] An increase in daily physical activity was considered to have a sustained bolstering effect on mental health.

Green tea extracts reduce leukocyte cell-Derived chemotaxin 2 and selenoprotein P levels in the livers of C57BL/6J mice fed a high-fat diet.

Epidemiological studies suggest that green tea extracts (GTEs), including catechins such as epigallocatechin gallate and epicatechin gallate, have a beneficial effect on obesity, hyperglycemia, insulin resistance, endothelial dysfunction, and inflammation. Although several studies have shown that catechins directly modulate the cellular and molecular alterations in the liver tissue, the contributions of indirect mechanisms underlying these systemic effects of catechins remain unclear. In this study, we report that, in the C57BL/6J mouse liver, GTEs reduce high-fat diet-induced increases in the levels of hepatokines, liver-derived secretary proteins such as leukocyte cell-derived chemotaxin 2 and selenoprotein P production, which have been shown to induce systemic adverse effects, including several metabolic diseases. These findings suggest that the systemic effects of GTEs involve the regulation of hepatokine production as an indirect mechanism.

Green tea extracts ameliorate high-fat diet-induced muscle atrophy in senescence-accelerated mouse prone-8 mice.

Muscle atrophy (loss of skeletal muscle mass) causes progressive deterioration of skeletal function. Recently, excessive intake of fats was suggested to induce insulin resistance, followed by muscle atrophy. Green tea extracts (GTEs), which contain polyphenols such as epigallocatechin gallate, have beneficial effects on obesity, hyperglycemia, and insulin resistance, but their effects against muscle atrophy are still unclear. Here, we found that GTEs prevented high-fat (HF) diet-induced muscle weight loss in senescence-accelerated mouse prone-8 (SAMP8), a murine model of senescence. SAMP8 mice were fed a control diet, an HF diet, or HF with 0.5% GTEs (HFGT) diet for 4 months. The HF diet induced muscle weight loss with aging (measured as quadriceps muscle weight), whereas GTEs prevented this loss. In HF diet-fed mice, blood glucose and plasma insulin concentrations increased in comparison with the control group, and these mice had insulin resistance as determined by homeostasis model assessment of insulin resistance (HOMA-IR). In these mice, serum concentrations of leukocyte cell-derived chemotaxin 2 (LECT2), which is known to induce insulin resistance in skeletal muscle, were elevated, and insulin signaling in muscle, as determined by the phosphorylation levels of Akt and p70 S6 kinases, tended to be decreased. In HFGT diet-fed mice, these signs of insulin resistance and elevation of serum LECT2 were not observed. Although our study did not directly show the effect of serum LECT2 on muscle weight, insulin resistance examined using HOMA-IR indicated an intervention effect of serum LECT2 on muscle weight, as revealed by partial correlation analysis. Accordingly, GTEs might have beneficial effects on age-related and HF diet-induced muscle weight loss, which correlates with insulin resistance and is accompanied by a change in serum LECT2.

Foot pressure analysis of gait pattern in older Japanese females requiring different personal care support levels.

[Purpose] This study evaluated gait parameters and foot pressure in two regions of the feet among older females with different personal care support needs to analyze factors that contribute to higher support requirements. [Subjects and Methods] Thirty-two older females were divided into support-need and care-need level groups. Gait parameters (speed, cadence, step length, step width, gait angle, toe angle, double support phase, swing phase, and stance phase) and foot pressure during a 5-m walk were measured and analyzed in the two groups. [Results] The percentage of the double support phase on both feet and the right stance phase were significantly higher in the care-need level group, while that of the right swing phase was significantly lower than that of the support-need level group. Additionally, the phase showing peak pressure on the left rear foot was significantly delayed and the left forefoot pressure in the terminal stance was significantly lower in the care-need level group than in the support-need level group. [Conclusion] These findings show that the temporal duration parameters and foot pressure on a particular side were significantly different between the two groups and suggest that these differences were associated with a higher care level.

Effects of exercise and tea catechins on muscle mass, strength and walking ability in community-dwelling elderly Japanese sarcopenic women: a randomized controlled trial.

AIM: To investigate the effects of exercise and/or tea catechin supplementation on muscle mass, strength and walking ability in elderly Japanese women with sarcopenia. METHODS: A total of 128 women aged over 75 years were defined as sarcopenic and randomly assigned into four groups: exercise and tea catechin supplementation (n = 32), exercise (n = 32), tea catechin supplementation (n = 32) or health education (n = 32). The exercise group attended a 60-min comprehensive training program twice a week and the tea catechin supplementation group ingested 350 mL of a tea beverage fortified with catechin daily for 3 months. Body composition was determined by bioelectrical impedance analysis. Interview data and functional fitness measurements, such as muscle strength, balance and walking ability, were collected at baseline and after the 3-month intervention. RESULTS: There were significant group × time interactions observed in timed up & go (P < 0.001), usual walking speed (P = 0.007) and maximum walking speed (P < 0.001). The exercise + catechin group showed a significant effect (odds ratio 3.61, 95% confidence interval 1.05-13.66) for changes in the combined variables of leg muscle mass and usual walking speed compared with the health education group. CONCLUSIONS: The combination of exercise and tea catechin supplementation had a beneficial effect on physical function measured by walking ability and muscle mass.

The short-term effect of diacylglycerol oil consumption on total and dietary fat utilization in overweight women.

Diacylglycerol (DAG) is a natural component of edible oils with metabolic characteristics distinct from those of triacylglycerol (TAG). Consumption of DAG oil (containing > 80% DAG) induces greater fat oxidation than consumption of TAG oil. We compared the effects of 4 days of DAG oil consumption with those of TAG oil consumption on total and dietary fat oxidation over 24 h in overweight women using a whole-room respiratory chamber. Overweight (BMI (kg/m²) ≥ 25) females participated in this double-blind, crossover-controlled trial. The subjects consumed test diets containing either TAG or DAG oil as 15% of their total caloric intake (mean test oil intake was 33.0 ± 3.1 g/day) during each 4-day treatment. Fat oxidation and energy expenditure were measured in a respiratory chamber on the 4th day of each treatment. Compared with TAG oil, DAG oil consumption significantly increased total fat oxidation and dietary fat oxidation in overweight subjects. Total energy expenditure (TEE) and carbohydrate (CHO) oxidation did not significantly differ between DAG oil and TAG oil consumption in overweight subjects. Compared with TAG oil, DAG oil consumption enhanced total fat oxidation and dietary fat oxidation in overweight subjects. The enhanced fat metabolism in overweight subjects that consumed DAG oil partly explains the greater loss of body weight and body fat related to DAG oil consumption in weight-loss studies.

Green tea catechins improve human forearm vascular function and have potent anti-inflammatory and anti-apoptotic effects in smokers.

OBJECTIVE: Several epidemiological investigations have reported that green tea reduces cardiovascular and cerebral vascular risks. Green tea catechins may improve peripheral endothelial dysfunction in smokers. The purpose of this study was to elucidate the beneficial effect of green tea catechins on the repair of endothelial dysfunction in smokers. METHODS: Thirty healthy male smokers divided into three groups ingested a green tea beverage containing 0 mg (control group), 80 mg (middle dose group) or 580 mg (high dose group) of green tea catechins (GTC) daily for two weeks, and endothelial-dependent vasodilatation was investigated by measuring forearm blood flow (FBF) response to reactive hyperemia (RH) by venous occlusion strain-gauge plethysmography. RESULTS: An acute effect was that the FBF response to RH significantly increased 2 hr after GTC intake in the high dose group. However, no increase was observed in the other groups. The chronic administration of GTC for one or two weeks ameliorated the FBF responses to RH in the high dose group. On the other hand, no significant increase was observed in the FBF responses to RH in the other groups. Moreover, the plasma concentration of 8-OHdG, IL-6, TNF-alpha, and soluble Fas decreased significantly for two weeks in the high dose group, however, the level of IL-1 beta remained unchanged over this period. CONCLUSION: Green tea consumption over short and long periods appears to ameliorate endothelial dysfunction by scavenging free radicals with anti-inflammatory and anti-apoptotic properties in healthy male smokers.

Green tea catechins improve human forearm endothelial dysfunction and have antiatherosclerotic effects in smokers.

BACKGROUND: Because green tea reduces cardiovascular and cerebrovascular risk, the purpose of this study aimed to elucidate the effect of green tea catechins (GTC) on endothelial dysfunction in smokers. METHODS AND RESULTS: The 30 healthy male smokers were divided into 3 groups and given green tea beverages containing 0 mg (control group), 80 mg (medium-dose group) or 580 mg (high-dose group) of GTC daily for 2 weeks. Endothelial-dependent and- independent vasodilatation was investigated by measuring the forearm blood flow (FBF) responses to acetylcholine and sodium nitroprusside using venous occlusion strain-gauge plethysmography. The FBF response to acetylcholine significantly increased at 2 h and 1 and 2 weeks after GTC intake in the high-dose group, but no increase was observed in the other groups. FBF responses to sodium nitroprusside did not alter in any group at any time point. A significant increase in plasma nitric oxide and a decrease in asymmetrical dimethylarginine, malondealdehyde and 4-hydroxynonenal, C-reactive protein, monocyte chemotactic protein-1, and soluble CD40 ligand levels were detected after chronic consumption of high-dose GTC. CONCLUSIONS: GTC have antiatherosclerotic effects on dysfunctional vessels in smokers through increasing the level of nitric oxide and reducing oxidative stress.

RS4-type resistant starch prevents high-fat diet-induced obesity via increased hepatic fatty acid oxidation and decreased postprandial GIP in C57BL/6J mice.

Chemically modified starches (CMS) are RS4-type resistant starch, which shows a reduced availability, as well as high-amylose corn starch (HACS, RS2 type), compared with the corresponding unmodified starch. Previous studies have shown that RS4 increases fecal excretion of bile acids and reduces zinc and iron absorption in rats. The aim of this study was to investigate the effects of dietary RS4 supplementation on the development of diet-induced obesity in mice. Weight- and age-matched male C57BL/6J mice were fed for 24 wk on a high-fat diet containing unmodified starch, hydroxypropylated distarch phosphate (RS4), or HACS (RS2). Those fed the RS4 diet had significantly lower body weight and visceral fat weight than those fed either unmodified starch or the RS2 diet. Those fed the RS4 diet for 4 wk had a significantly higher hepatic fatty acid oxidation capacity and related gene expression and lower blood insulin than those fed either unmodified starch or the RS2 diet. Indirect calorimetry showed that the RS4 group exhibited higher energy expenditure and fat utilization compared with the RS2 group. When gavaged with fat (trioleate), RS4 stimulated a lower postprandial glucose-dependent insulinotropic polypeptide (GIP; incretin) response than RS2. Higher blood GIP levels induced by chronic GIP administration reduced fat utilization in high-fat diet-fed mice. In conclusion, dietary supplementation with RS4-type resistant starch attenuates high-fat diet-induced obesity more effectively than RS2 in C57BL/6J mice, which may be attributable to lower postprandial GIP and increased fat catabolism in the liver.

Effects of hydroxyhydroquinone-reduced coffee on vasoreactivity and blood pressure.

Recent studies suggest that chlorogenic acids, which are the main components of the polyphenol class in coffee, decrease blood pressure, and that hydroxyhydroquinone (HHQ), which is generated by roasting coffee beans, inhibits the antihypertensive effect of chlorogenic acids in brewed coffee. Here, we examined the vasoreactivity and antihypertensive effects of HHQ-reduced coffee in mild hypertension. The study design was a double blind, randomized, placebo-controlled intervention study, with a 4-week run-in period, followed by an 8-week test beverage ingestion period. The subjects were Japanese men and women with mild hypertension and vascular failure, who were not taking any antihypertensive drugs. During the test beverage ingestion period, the subjects ingested either active or placebo HHQ-reduced coffee (chlorogenic acids per 184 ml of coffee: active, 300 mg; and placebo, 0 mg) daily. Subjects were randomly divided into two groups: active group (n=9) and placebo group (n=12). In the active beverage group, endothelium-dependent, flow-mediated vasodilation impairment was significantly ameliorated and systolic blood pressure was significantly decreased from the baseline, but not in the placebo group. There were no test beverage consumption-related changes in other parameters that may influence blood pressure, such as pulse, cardiac output, body weight or 24-h urine volume. Ingestion of the active beverage significantly decreased urinary isoprostane levels, suggesting a reduced oxidative stress. These findings indicate that HHQ-reduced coffee decreased blood pressure in subjects with mild hypertension. The decreased blood pressure was associated with improved vascular endothelial function.

Effectiveness and safety of 1-year ad libitum consumption of a high-catechin beverage under nutritional guidance.

BACKGROUND: It has been reported that a continuous intake of a catechin beverage will reduce body fat. Traditionally, improvement of eating and exercise habits has been the basis for prevention and reduction of obesity. In this study, we conducted a trial involving human subjects who ingested a catechin beverage for 1 year under nutritional guidance. METHODS: This study was conducted based on a comprehensive cohort design using a catechin beverage (containing 588 mg of tea catechins) and a control beverage (containing 126 mg of tea catechins). At both the start and the end of the trial, the subjects underwent an annual health check and computer tomography for measurement of their abdominal fat. In addition, a food intake survey was conducted and all subjects were provided nutritional guidance by a registered dietitian every 3 months. RESULTS: Data were analyzed using per protocol samples of 134 subjects (catechin group, n = 77; control group, n = 57). Body weight and body mass index were reduced significantly in the catechin group compared to the control group. Changes in body weight during the study period were -1.1 kg in the catechin group and 0.2 kg in the control group. In the catechin group, the visceral fat areas at the start of the trial were significantly correlated with the magnitude of fat reduction at the end of the trial. Under the guidance of a registered dietitian, subjects in the catechin group who showed a reduction in their fat-derived energy percentage during the test period tended to reduce more body weight than those with an increase in this percentage, although no difference in total energy intake was noted between the two groups. One-year ad libitum consumption of a catechin beverage posed no health risks and resulted in a reduction in body weight. CONCLUSIONS: An overall improvement in dietary habits might enhance the weight-reduction effect of the beverage.

Body fat mass reduction and up-regulation of uncoupling protein by novel lipolysis-promoting plant extract.

We have found natural products exhibiting lipolysis-promoting activity in subcutaneous adipocytes, which are less sensitive to hormones than visceral adipocytes. The activities and a action mechanisms of a novel plant extract of Cirsium oligophyllum (CE) were investigated in isolated adipocytes from rat subcutaneous fat, and its fat-reducing effects by peroral administration and topical application were evaluated in vivo. CE-induced lipolysis was synergistically enhanced by caffeine, a phosphodiesterase inhibitor, and was reduced by propranolol, a beta adrenergic antagonist. The peroral administration of 10% CE solution to Wistar rats for 32 days reduced body weight gain, subcutaneous, and visceral fat weights by 6.6, 26.2, and 3.0%, respectively, as compared to the control group. By the topical application of 2% of this extract to rats for 7 days, weight of subcutaneous fat in the treated skin was reduced by 23.2%. This fat mass reduction was accompanied by the up-regulation of uncoupling protein 1 (UCP), a principal thermogenic mitochondrial molecule related to energy dissipating, in subcutaneous fat and UCP3 in skin except for the fat layer. These results indicate that CE promotes lipolysis via a mechanism involving the beta adrenergic receptor, and affects the body fat mass. This fat reduction may be partially due to UCP up-regulation in the skin including subcutaneous fat. This is the first report showing that repeated lipolysis promotion through CE administration may be beneficial for the systematic suppression of body fat accumulation or the control of fat distribution in obesity.

The effects of diacylglycerol oil on fat oxidation and energy expenditure in humans and animals.

Studies in animals and humans indicate that diets containing diacylglycerol (DAG) oil (containing >80% DAG) decrease body weight gain and body fat accumulation, especially visceral fat. Body weight and body fat are controlled by energy expenditure, fat oxidation, fat storage capacity, and appetite control. Recent researches indicate that DAG oil, compared with conventional oils, has distinct metabolic effects. We review the evidence concerning the effects of DAG oil intake on fat oxidation and energy expenditure. In humans, dietary DAG is more susceptible to oxidation, and in animals 1,3-DAG, a major component of DAG oil, is rapidly oxidized. Short-term human studies with indirect calorimetry demonstrate greater fat oxidation with DAG oil consumption compared with triacylglycerol (TAG) oil consumption. Furthermore, DAG oil consumption for 14 days stimulates energy expenditure. Based on these reports, enhanced fat oxidation and energy expenditure by daily DAG oil intake could contribute to long-term reductions in body weight and fat accumulation. The literature provides support for the notion that dietary DAG is more rapidly oxidized than dietary TAG, and that, compared with TAG oil, DAG oil consumption increases whole body fat oxidation. The effects of DAG oil consumption on energy expenditure, however, remain inconclusive. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.

Coingestion of acylglycerols differentially affects glucose-induced insulin secretion via glucose-dependent insulinotropic polypeptide in C57BL/6J mice.

The precise role of fat in postprandial glycemia and insulinemia has not been thoroughly researched because postprandial blood glucose and concurrent insulin secretion are largely assumed to be proportional to carbohydrate intake. Recent studies have suggested that dietary fat differentially regulates the postprandial insulin response. To explore this, we examined the effects of coadministered fat on glucose-induced glycemia and insulinemia in C57BL/6J mice. The insulin response to glucose was augmented by the addition of glycerol trioleate (TO) in a dose-dependent manner, which was associated with enhanced glucose transport from the circulation to muscle and adipose tissues. To investigate the mechanism underlying fat-induced hyperinsulinemia, we examined the release of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1. TO increased GIP secretion, whereas glucagon-like peptide-1 secretion was unaffected. TO-induced hyperinsulinemia was significantly attenuated by the pretreatment of mice with a specific GIP antagonist. Diacylglycerol (DAG) promoted lower postprandial GIP and triglyceride responses and, when ingested with glucose, a lower insulin response compared with triacylglycerol of a similar fatty acid composition. Pluronic L-81, an inhibitor of chylomicron formation, reduced not only the triglyceride response but also TO-induced GIP secretion, indicating that the lower GIP response after DAG ingestion may be associated with retarded chylomicron formation in the small intestine. We conclude that dietary fat augments glucose-induced insulinemia via gut-derived GIP and, thereby, influences postprandial nutrient metabolism in mice. DAG promotes a lower GIP and thereby reduced insulin responses compared with triacylglycerol, which may differentially influence postprandial energy homeostasis.

Different contribution of muscle and liver lipid metabolism to endurance capacity and obesity susceptibility of mice.

We investigated strain differences in whole body energy metabolism, peripheral lipid metabolism, and energy metabolism-related gene expression and protein levels in BALB/c, C57BL/6J, and A/J mice to evaluate the relationship between endurance capacity, susceptibility to diet-induced obesity, and differences in lipid metabolism in muscle and liver. A high-fat diet significantly increased body weight and fat weight in C57BL/6J mice, but not in BALB/c and A/J mice. The endurance capacity of BALB/c mice was 52% greater than that of C57BL/6J mice and 217% greater than that of A/J mice. The respiratory exchange ratio was lowest in BALB/c mice, higher in C57BL/6J mice, and highest in A/J mice, which inversely correlated with the endurance capacity and fatty acid beta-oxidation activity in the muscle. Plasma lactate levels measured immediately after exercise were lowest in BALB/c mice and highest in A/J mice, although there was no difference under resting conditions, suggesting that carbohydrate breakdown is suppressed by enhanced fat utilization during exercise in BALB/c mice. On the other hand, the body weight increase induced by high-fat feeding was related to a reduced whole body energy expenditure, higher respiratory quotient, and lower fatty acid beta-oxidation activity in the liver. In addition, beta-oxidation activity in the muscle and liver roughly paralleled the mRNA and protein levels of lipid metabolism-related molecules, such as peroxisome proliferator-activated receptor and medium-chain acyl-CoA dehydrogenase, in each tissue. These findings indicate that genetically determined basal muscle and liver lipid metabolism and responsiveness to exercise influence physical performance and obesity susceptibility.

Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults.

This study evaluated the influence of a green tea catechin beverage on body composition and fat distribution in overweight and obese adults during exercise-induced weight loss. Participants (n = 132 with 107 completers) were randomly assigned to receive a beverage containing approximately 625 mg of catechins with 39 mg caffeine or a control beverage (39 mg caffeine, no catechins) for 12 wk. Participants were asked to maintain constant energy intake and engage in >or=180 min/wk moderate intensity exercise, including >or=3 supervised sessions per week. Body composition (dual X-ray absorptiometry), abdominal fat areas (computed tomography), and clinical laboratory tests were measured at baseline and wk 12. There was a trend (P = 0.079) toward greater loss of body weight in the catechin group compared with the control group; least squares mean (95% CI) changes, adjusted for baseline value, age, and sex, were -2.2 (-3.1, -1.3) and -1.0 (-1.9, -0.1) kg, respectively. Percentage changes in fat mass did not differ between the catechin [5.2 (-7.0, -3.4)] and control groups [-3.5 (-5.4, 1.6)] (P = 0.208). However, percentage changes in total abdominal fat area [-7.7 (-11.7, -3.8) vs. -0.3 (-4.4, 3.9); P = 0.013], subcutaneous abdominal fat area [-6.2 (-10.2, -2.2) vs. 0.8 (-3.3, 4.9); P = 0.019], and fasting serum triglycerides (TG) [-11.2 (-18.8, -3.6) vs. 1.9 (-5.9, 9.7); P = 0.023] were greater in the catechin group. These findings suggest that green tea catechin consumption enhances exercise-induced changes in abdominal fat and serum TG.

A catechin-rich beverage improves obesity and blood glucose control in patients with type 2 diabetes.

We investigated the effects of continuous ingestion of a catechin-rich beverage in patients with type 2 diabetes who were not receiving insulin (Ins) therapy in a double-blind controlled study. The participants ingested green tea containing either 582.8 mg of catechins (catechin group; n = 23) or 96.3 mg of catechins (control group; n = 20) per day for 12 weeks. At week 12, the decrease in waist circumference was significantly greater in the catechin group than in the control group. Adiponectin, which is negatively correlated with visceral adiposity, increased significantly only in the catechin group. Although the increase in Ins at week 12 was significantly greater in the catechin group than in the control group, no apparent difference was noted between the two groups in glucose and hemoglobin A(1c). In patients treated with insulinotropic agents, the increase in Ins at week 12 was significantly greater in the catechin group than in the control group. This significant increase in Ins levels was observed only in the catechin group. In the catechin group receiving other treatments, Ins levels remained unchanged. In addition, in patients treated with insulinotropic agents, the decrease in hemoglobin A(1c) at week 12 was significantly greater in the catechin group than in the control group. These results suggest that a catechin-rich beverage might have several therapeutic uses: in the prevention of obesity; in the recovery of Ins-secretory ability; and, as a way to maintain low hemoglobin A(1c) levels in type 2 diabetic patients who do not yet require Ins therapy.

Effects of coumestrol on lipid and glucose metabolism as a farnesoid X receptor ligand.

In the course of an effort to identify novel agonists of the farnesoid X receptor (FXR), coumestrol was determined to be one such ligand. Reporter and in vitro coactivator interaction assays revealed that coumestrol bound and activated FXR. Treatment of Hep G2 cells with coumestrol stimulated the expression of FXR target genes, thereby regulating the expression of target genes of the liver X receptor and hepatocyte nuclear factor-4alpha. Through these actions, coumestrol is expected to exert beneficial effects on lipid and glucose metabolism.