Preventive Effect of Boiogito on Metabolic Disorders in the TSOD Mouse, a Model of Spontaneous Obese Type II Diabetes Mellitus

“Boiogito” is a Kampo preparation which has been used since ancient times in patients with obesity of the “asthenic constitution” type, so-called “watery obesity”, and its effect has been recognized clinically. In this study, we investigated the anti-obesity effect of Boiogito in the TSOD (Tsumura Suzuki Obese Diabetes) mouse, a model of spontaneous obese type II diabetes mellitus. Boiogito showed a significant anti-obesity effect in TSOD mice by suppressing body weight gain in a dosage-dependent manner. In addition, Boiogito showed significant ameliorative effects on features of metabolic syndrome such as hyperinsulinemia, fasting hyperglycemia and abnormal lipid metabolism. Regarding lipid accumulation in TSOD mice, Boiogito showed a significant suppressive effect on accumulation of subcutaneous fat, but the effect on the visceral fat accumulation that constitutes the basis of metabolic syndrome was weak, and the suppressive effect on insulin resistance was also weak. Furthermore, Boiogito did not alleviate the abnormal glucose tolerance, the hypertension or the peripheral neuropathy characteristically developed in the TSOD mice. In contrast, in the TSNO (Tsumura Suzuki Non-Obesity) mice used as controls, Boiogito suppressed body weight gain and accumulation of subcutaneous and visceral fat. The above results suggested that Boiogito is effective as an anti-obesity drug against obesity of the “asthenic constitution” type in which subcutaneous fat accumulates, but cannot be expected to exert a preventive effect against various symptoms of metabolic syndrome that are based on visceral fat accumulation

Preventive Effect of Pine Bark Extract (Flavangenol) on Metabolic Disease in Western Diet-Loaded Tsumura Suzuki Obese Diabetes Mice

It is known that the metabolic syndrome has a multi-factorial basis involving both genetic and environmental risk factors. In this study, Tsumura Suzuki Obese Diabetes (TSOD) mice, a mouse model of multi-factorial, hereditary, obese type II diabetes, were given a Western diet (WTD) as an environmental factor to prepare a disease model (TSOD-WTD) and to investigate the preventive effects of Pine bark extract (Flavangenol) against obesity and various features of metabolic disease appearing in this animal model. In contrast to control Tsumura Suzuki Non-obesity (TSNO) mice, TSOD mice were obese and suffered from other metabolic complications. WTD-fed TSOD mice developed additional features such as hyperinsulinemia, abnormal glucose/lipid metabolism and fatty liver. The treatment with Flavangenol had a suppressive effect on increase in body weight and accumulation of visceral and subcutaneous fat, and also showed preventive effects on symptoms related to insulin resistance, abnormal glucose/lipid metabolism and hypertension. Flavangenol also increased the plasma concentration of adiponectin and decreased the plasma concentration of TNF-α. We next investigated the effect of Flavangenol on absorption of meal-derived lipids. Flavangenol suppressed absorption of neutral fat in an olive-oil-loading test (in vivo) and showed an inhibitory effect on pancreatic lipase (in vitro). The above results suggest that Flavangenol has a preventive effect on severe metabolic disease due to multiple causes that involve both genetic and environmental risk factors. The mechanism of action might involve a partial suppressive effect of meal-derived lipids on absorption

The effects of resistive exercise with low intensity-high frequency on essential mild hypertension in men

高血圧症は心筋梗塞, 脳卒中, 動脈硬化の独立した危険因子になっている。日本人30歳以上の成人男子の約48%が軽症を含めた高血圧症とされている。高血圧関連疾患や死亡の予防として軽症高血圧症時の血圧コントロールは重要な関心点である。薬物による高血圧治療は著しい効果をあげているが, 好ましくない副作用の発現も見逃せない。薬物療法に対して運動療法が近年広く処方されるようになってきた。これまでに多くの研究が有酸素運動の降圧効果を報告しているが, レジスタンス運動による降圧効果については異なる知見が出されている。そこで本研究においては, 有酸素運動の様式に似た低強度-高頻度レジスタンス運動を用いて中年軽症高血圧男子に対する降圧効果を検索した。方法。42歳-56歳 (平均48.3) の男子10名が被検者として参加し, 内5名がレジスタンス運動群 (RE) に他の5名がウオーキング群 (AE) に区分された。RE群は10種目のウエイト運動を最大筋力の40-50%強度, 20-25レペテイションで2-3セット, 週3回の形で12週間行った。一方のAE群は同様に予測最大心拍数の60-75%強度の30分速歩を週3回, 12週間行った。結果。安静時血圧においてRE群はAE群より程度は低いものの有意な (P値2.3ml/kg/min=6.9%) と身体組成の改善 (体脂肪1.5kg=8.8%減) が見られ, その改善率はAE群に比べて小さいがいずれも有意であった (AE群 : 6ml/kg/min=17%, 3.1kg=18.9%)。また, 体重もしくは体脂肪の減少量と降圧値との間には有意差が得られなかったが相関傾向が見られた。しかし, AE群と異なり, RE群では血清総コレステロール, 高比重リポ蛋白コレステロール, 低比重リポ蛋白コレステロール, トリグリセライド (中性脂肪) の血清脂質・リポ蛋白濃度の有意な改善は見られなかった。結語。これまで血圧や身体組成もしくは有酸素性体力の改善, 向上に対するレジスタンス運動の効果については意見の一致をみていない。考えられる要因の一つに運動の処方の違いが挙げられる。血圧や身体組成の改善に対しては低強度・高頻度による運動量負荷 (Volume loading) の処方が好ましく, 高強度による過重負荷 (Over-weight loading) は至適処方とは言えないであろう。今回の研究においてレジスタンス運動による血清脂質の有意な改善が見られなかったのは総運動量が十分な刺激とならなかったものと考えられる。本研究は低強度高頻度のレジスタンス運動の習慣化が軽症高血圧患者の健康改善に効果的であることを示唆するものである。Five sedentary middle-aged men with mild hypertension were studied to determine the effects of a low-to moderate-intensity resistive exercise program (RE group) on resting systolic and diastolic blood pressures. Another group of five mild hypertensive men was also examined to determine the effects of a moderate aerobic exercise program (AE group) on the resting blood pressures. Besides blood pressures, effects of respective training programs were studied on aerobic capacity, muscle strengths, and serum lipid and lipoprotein concentrations. Resistive exercise consisted of 10 stations of weight training machines for 12 weeks. Workloads were set at 40-50% maximum and the subjects performed 10 repetitions for each station with 2-3 sets, 3 times per week. The subjects in the aerobic exercise group performed 30-min brisk waking or jogging with intensities of 60-75% their predicted maximum heart rates. The following changes occurred in the resistive exercise group : (1) resting systolic blood pressure dropped significantly (from 150 to 143mm Hg) after training and diastolic blood pressure dropped significantly (from 91 to 88mm Hg) after training ; (2) VO_ significantly increased 2.3 ml/kg/min or 6.9% (from 33.3 to 35.6 ml/kg/min) after training ; (3) increases of muscle strengths were profound, 17.9% and 23% in lower and upper body strengths, respectively ; (4) body weight and body fat decreased 2.6% (P) as well as body composition. Serum lipid lipoproteins included total cholesterol (TC), high-density cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Significant (P<0.01) increase was noted for HDL-C while significant decreases were seen in TC, LDL-C, and TG

Preventive effects of Daisaikoto on metabolic disorders in spontaneous obese type II diabetes mice

メタボリックシンドローム(MS)は，生活習慣病の基礎病態として特に注目されている症候群の一つである。近年，肥満人口は増加の一途をたどっているが，内臓脂肪の蓄積はMSの病態基盤として最も重要な危険因子であることが報告されている。本研究においては，MS類似病態を発症する肥満性2型糖尿病モデル動物であるTSODマウスを用い，諸代謝性疾病に対する漢方薬大柴胡湯の効果を検討した。肥満が未発症の４週齢TSODマウスおよび代謝性疾病を発症しないTSNOマウスに大柴胡湯を1％および3％混和させた粉末飼料を2ヶ月間自由摂取させた。その結果，普通食摂餌TSODマウスは，試験開始後より普通食摂餌TSNOマウスに比べ著しい肥満および内臓脂肪の蓄積，血糖値，インスリン値，T-Cho値，TG値およびLDL値の上昇，耐糖能異常などを発症し，さらに高血圧および末梢神経障害が認められた。TSODマウスにおいて，大柴胡湯は投与後期より体重増加や内臓脂肪の蓄積等に対して低下作用を与え，さらに，耐糖能異常，血圧の上昇や末梢神経障害を有意に抑制した。以上より，MS諸症状に対する大柴胡湯の有用性が示唆された。 Metabolic syndrome (MS) is one of the syndromes known as an underlying lifestyle-related diseases. Recently, the number of obese people keeps on increasing, and visceral fat accumulation has been reported as the most important risk factor for the development of MS. In this study, the effects of Daisaikoto, a Kampo preparation, on metabolic disorders were investigated using TSOD mice, an animal model of spontaneous obese type II diabetes. Four-week-old TSOD mice that had not yet developed obesity and TSNO mice that do not develop metabolic disorders were given ad libitum powder feed containing Daisaikoto at a concentration of 1% or 3% for 2 months. After 2 months, the control TSOD mice developed various metabolic disorders such as marked obesity and visceral fat accumulation, increase of the blood glucose level, the insulin level, T-Cho level, TG level and LDL level, abnormal glucose tolerance, hypertension and neuropathy as distinct from the control TSNO mice. In the TSOD mice treated with Daisaikoto, the body weight gain and visceral fat accumulation were suppressed, and the abnormal glucose tolerance, elevation of blood pressure and peripheral neuropathy were also significantly suppressed. On the other hand, in TSNO mice, Daisaikoto showed no noteworthy impacts on most parameters. The above results suggested that Daisaikoto would be effective for the prevention against various symptoms of MS

Reactive Sulfur Species Interact with Other Signal Molecules in Root Nodule Symbiosis in Lotus japonicus

Reactive sulfur species (RSS) function as strong antioxidants and are involved in various biological responses in animals and bacteria. Few studies; however, have examined RSS in plants. In the present study, we clarified that RSS are involved in root nodule symbiosis in the model legume Lotus japonicus. Polysulfides, a type of RSS, were detected in the roots by using a sulfane sulfur-specific fluorescent probe, SSP4. Supplying the sulfane sulfur donor Na2S3 to the roots increased the amounts of both polysulfides and hydrogen sulfide (H2S) in the roots and simultaneously decreased the amounts of nitric oxide (NO) and reactive oxygen species (ROS). RSS were also detected in infection threads in the root hairs and in infected cells of nodules. Supplying the sulfane sulfur donor significantly increased the numbers of infection threads and nodules. When nodules were immersed in the sulfane sulfur donor, their nitrogenase activity was significantly reduced, without significant changes in the amounts of NO, ROS, and H2S. These results suggest that polysulfides interact with signal molecules such as NO, ROS, and H2S in root nodule symbiosis in L. japonicus. SSP4 and Na2S3 are useful tools for study of RSS in plants