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

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