Tadashi Hase

A Green Tea Extract High in Catechins Reduces Body Fat and Cardiovascular Risks in Humans

Objective: The body fat reducing effect and reduction of risks for cardiovascular disease by a green tea extract (GTE) high in catechins was investigated in humans with typical lifestyles.

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 A1c. 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 A1c 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 A1c levels in type 2 diabetic patients who do not yet require Ins therapy.

Short chain fatty acids but not lactate or succinate stimulate mucus release in the rat colon

BACKGROUND Short chain fatty acids (SCFAs) affect various intestinal functions. Mucus is an important physiological component of the intestinal mucosal barrier. However, the effect of SCFAs or other organic acids on the intestinal mucus release is poorly understood. The aim of this study was to investigate whether lumen SCFA stimulates mucus release into the rat colon. METHODS A solution of SCFA, lactate or succinate was infused into the colon of anesthetized rats, and we then measured the hexose content of the effluent. We also examined the influence of cholinergic antagonists on the effects of SCFA. RESULTS A SCFA mixture (75 mM acetate, 35 mM propionate and 20 mM butyrate) or individual SCFAs (130 mM) increased the mucus release into the colon in a similar manner. The individual SCFAs, but not lactate or succinate, stimulated colonic mucus secretion in similar concentration-dependent manners. Butyrate stimulated colonic mucus secretion at 20 mM, but acetate, propionate, lactate and succinate at this concentration did not. Pretreatment with an anti-cholinergic agent diminished the stimulatory effects of SCFAs on mucus secretion. CONCLUSIONS Lumen SCFAs, but not lactate or succinate, stimulate mucus release from the rat colon via a cholinergic nerve mechanism.

Catechin-induced activation of the LKB1/AMP-activated protein kinase pathway.

Catechins are abundant in green tea and induce a variety of biologic actions, including anti-cancer, anti-obesity, and anti-diabetes effects, and their clinical application has been widely investigated. To clarify the underlying molecular mechanisms of these actions, we examined the effect of catechins on AMP-activated protein kinase (AMPK) in cultured cells and in mice. In Hepa 1-6, L6, and 3T3-L1 cells, epigallocatechin gallate (EGCG) induced increases in AMPKalpha and the downstream target acetyl-CoA carboxylase (ACC) phosphorylation, and AMPKalpha activity. Analysis of the molecular specificity of eight naturally occurring catechins revealed that catechins with a gallocatechin moiety or a galloyl residue act as AMPK activators. In addition, phosphorylation of LKB1, which is a tumor-suppressor protein and a major AMPK-kinase, was increased by catechin treatment. EGCG-induced phosphorylation of LKB1 and AMPKalpha was suppressed by treatment with catalase, suggesting that reactive oxygen species are involved in EGCG-induced activation of the LKB1/AMPK pathway. Oral administration of EGCG (200mg/kg body weight) to BALB/c mice induced an increase in AMPKalpha activity in the liver concomitant with a significant increase in AMPKalpha and ACC phosphorylation. EGCG administration also increased oxygen consumption and fat oxidation, as determined by indirect calorimetry. These findings suggest that multiple effects of catechins, including anti-obesity and anti-cancer effects, are mediated, at least in part, by the activation of LKB1/AMPK in various tissues, and that these effects vary according to the catechin structure.

Digestion and assimilation features of dietary DAG in the rat small intestine.

Several recent studies have demonstrated that dietary DAG oil rich in 1,3-species suppresses the postprandial increase of serum TAG level and decreases body fat accumulation, compared with TAG oil. To clarify the mechanisms underlying the beneficial effects of DAG, we investigated the metabolic features of DAG in the small intestine with regard to the digestion pathway in the lumen and the TAG-synthesis pathway in the mucosa. When intraduodenally infused as an emulsion, TAG was digested to 1,2-DAG, 2-MAG, and FFA, whereas 1,3-DAG was digested to 1(3)-MAG and FFA. When assessed by the incorporation of [1-14C]linoleic acid in lipids, the mucosal TAG-synthesis was significantly reduced by DAG infusion compared with TAG infusion. However, the mucosal 1,3-DAG synthesis was remarkably increased in the DAG-infused rats. The total amount of mucosal 1,3-DAG was also increased (4.5-fold) after DAG infusion compared with that after TAG infusion. Next, we examined the synthesis pathway of 1,3-DAG. In cultures of the everted intestinal sacs, 1,3-DAG production required the presence of 1-MAG, suggesting that the 1,3-DAG synthesis was due to acylation of 1(3)-MAG in the DAG-infused rats. Furthermore, measurements of DAG acyltransferase activity indicated that 1,3-DAG was little utilized in TAG synthesis. These findings suggest that features of 1,3-DAG digestion and assimilation in the intestine may be responsible for the reduction of the postprandial serum TAG level by dietary DAG.

Antihypertensive Effect of Green Coffee Bean Extract on Mildly Hypertensive Subjects

A water-soluble green coffee bean extract (GCE) has been shown to be effective against hypertension in both spontaneously hypertensive rats and humans. This multicenter, randomized, double-blind, placebo-controlled, parallel group study evaluated the dose-response relationship of GCE in 117 male volunteers with mild hypertension. Subjects were randomized into four groups: a placebo and three drug groups that received 46 mg, 93 mg, or 185 mg of GCE once a day. After 28 days, systolic blood pressure (SBP) in the placebo, 46 mg, 93 mg, and 185 mg groups was reduced by −1.3±3.0 mmHg, −3.2±4.6 mmHg, −4.7±4.5 mmHg, and −5.6±4.2 mmHg from the baseline, respectively. The decreases in SBP in the 93 mg group (p<0.05) and the 185 mg group (p<0.01) were statistically significant compared with the placebo group. Diastolic blood pressure (DBP) in the placebo, 46 mg, 93 mg, and 185 mg groups was reduced by −0.8±3.1 mmHg, −2.9±2.9 mmHg, −3.2±3.2 mmHg, and −3.9±2.8 mmHg from the baseline, respectively, and significant effects were observed in the 93 mg group (p<0.05) and the 185 mg group (p<0.01) compared with the placebo group. Both blood pressures were significantly reduced in a dose-related manner by GCE (p<0.001). Adverse effects caused by GCE were not observed. The results suggested that daily use of GCE has a blood pressure-lowering effect in patients with mild hypertension.

Decreased colonic mucus in rats with loperamide-induced constipation

Constipation is a risk factor of colorectal cancer. Mucin is a major component of lumenal mucus, which protects the colorectal mucosa against mechanical and chemical damage. The aim of this study was to evaluate mucus production and to quantitate lumen mucus in a rat model of spastic constipation. We induced constipation with loperamide (1.5 mg/kg), and histochemically evaluated mucus production and the thickness of the mucus layer at the fecal surface. We quantitated the mucus attached to the mucosal surface using colonic perfusion with N-acetylcysteine. While more feces remained in the colon, there was less fecal excretion and lower fecal water content in loperamide-administered rats than in control rats. Crypt epithelial cells contained less mucus in constipated rats than in control rats. The mucus layer at the fecal surface was thinner and less mucus was recovered from the mucosal surface in constipated rats than in control rats. Mucus production of crypt epithelial cells and mucus at the fecal and mucosal surface were reduced by loperamide-induced constipation.

Effects of exercise and milk fat globule membrane (MFGM) supplementation on body composition, physical function, and hematological parameters in community-dwelling frail Japanese women: a randomized double blind, placebo-controlled, follow-up trial.

Objective To investigate the combined and separate effects of exercise and milk fat globule membrane (MFGM) supplementation on frailty, physical function, physical activity level, and hematological parameters in community-dwelling elderly Japanese women. Methods A total of 131 frail, elderly women over 75 years were randomly assigned to one of four groups: exercise and MFGM supplementation (Ex+MFGM), exercise and placebo (Ex+Plac), MFGM supplementation, or the placebo group. The exercise group attended a 60-minute training program twice a week for three months, and the MFGM group ingested 1g of the MFGM supplement in pill form, daily for 3 months. The primary outcome measure was change in frailty status based on Fried’s frailty phenotype. Secondary outcome measures included body composition, physical function and hematological parameters, and interview survey components assessing lifestyle factors. Participants were followed for 4 months post-intervention. Results Significant group×time interactions were observed for usual walking speed (P = 0.005), timed up & go (P<0.001), and insulin-like growth factor-binding protein 3 / insulin-like growth factor 1 ratio (P = 0.013). The frailty components revealed that weight loss, exhaustion, low physical activity, and slow walking speed were reversed, but low muscle strength did not significantly changed. Frailty reversal rate was significantly higher in the Ex+MFGM (57.6%) than in the MFGM (28.1%) or placebo (30.3%) groups at post-intervention (χ2 = 8.827, P = 0.032), and at the follow-up was also significantly greater in the Ex+MFGM (45.5%) and Ex+Plac (39.4%) groups compared with the placebo (15.2%) group (χ2 = 8.607, P = 0.035). The exercise+MFGM group had the highest odds ratio (OR) for frailty reversal at post-intervention and follow-up (OR = 3.12, 95% confidence interval (CI) = 1.13–8.60; and OR = 4.67, 95% CI = 1.45–15.08, respectively). Conclusion This study suggests that interventions including exercise and nutrition can improve frailty status. Statistically significant additive effects of MFGM with exercise could not be confirmed in this population, and further investigation in larger samples is necessary. Trial Registration The Japan Medical Association Clinical Trial Registry (JMACCT)JMA-IIA00069

Sulfated polysaccharides, but not cellulose, increase colonic mucus in rats with loperamide-induced constipation.

Colonic mucus is decreased in a rat model of spastic constipation, and some types of water-insoluble dietary fiber increase colonic mucus when consumed by rats for several weeks. However, little is known about the effect of water-soluble dietary fiber on the colonic mucus. The aim of the present study was to investigate the effect of various types of water-soluble dietary fiber on colonic mucus in a rat model of spastic constipation. Oral administration of 1.5 mg/day of carrageenan and chondroitin sulfate increased the fecal excretion, epithelial mucin production, thickness of the mucous layer, and amount of luminal mucus in loperamide-administered rats. Sodium alginate, 5 mg/day, thickened the mucus layer at the fecal surface. Cellulose, 5 mg/day, increased the fecal excretion but not the colonic mucus. Carrageenan, chondroitin sulfate, and sodium alginate, but not cellulose, increased colonic mucus in the rat model of spastic constipation.

Coffee polyphenols modulate whole-body substrate oxidation and suppress postprandial hyperglycaemia, hyperinsulinaemia and hyperlipidaemia

Postprandial energy metabolism, including postprandial hyperglycaemia, hyperinsulinaemia and hyperlipidaemia, is related to the risk for developing obesity and CVD. In the present study, we examined the effects of polyphenols purified from coffee (coffee polyphenols (CPP)) on postprandial carbohydrate and lipid metabolism, and whole-body substrate oxidation in C57BL/6J mice. In mice that co-ingested CPP with a lipid-carbohydrate (sucrose or starch)-mixed emulsion, the respiratory quotient determined by indirect calorimetry was significantly lower than that in control mice, whereas there was no difference in VO2 (energy expenditure), indicating that CPP modulates postprandial energy partitioning. CPP also suppressed postprandial increases in plasma glucose, insulin, glucose-dependent insulinotropic polypeptide and TAG levels. Inhibition experiments on digestive enzymes revealed that CPP inhibits maltase and sucrase, and, to a lesser extent, pancreatic lipase in a concentration-dependent manner. Among the nine kinds of polyphenols (caffeoyl quinic acids (CQA), di-CQA, feruloyl quinic acids (FQA)) contained in CPP, di-CQA showed more potent inhibitory activity than CQA or FQA on these digestive enzymes, suggesting a predominant role of di-CQA in the regulation of postprandial energy metabolism. These results suggest that CPP modulates whole-body substrate oxidation by suppressing postprandial hyperglycaemia and hyperinsulinaemia, and these effects are mediated by inhibiting digestive enzymes.