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In developed countries including Japan, in recent years, the incidence of obesity has sharply increased by the overintake of calorie-rich diet and exercise-lacking lifestyles. 1)Metabolic syndrome caused by obesity with abdominal adiposity especially is a strong risk factor for type 2 diabetes 2) and cardiovascular diseases.3) Obesity in humans generally involves the interaction of multiple genes and environmental factors.Pioglitazone, a thiazolidinedione that improves insulin resistance, has been widely used for the treatment of type 2 diabetes with obesity and insulin resistance. However, body weight gain is frequently observed in patients during the administration of pioglitazone. 4)On the other hand, metformin, a biguanide that improves insulin resistance similarly to pioglitazone, has been also widely used for the treatment of type 2 diabetes. It has been reported that obese patients with type 2 diabetes treated with metformin do not gain body weight; indeed many patients on this agent lose body weight by decreasing food consumption.5-8) However, the mechanisms by which metformin treatment causes reduction of food consumption and body weight loss are not fully clarified. It has been indicated that metformin increases plasma active glucagon-like peptide-1 (GLP-1) in obese nondiabetic subjects.9) GLP-1 is an incretin released from L cells in the intestine after oral ingestion of nutrients. This incretin has several actions such as stimulation of insulin biosynthesis, inhibition of glucagon secretion, and inhibition of gastric emptying in addition to promotion of satiety and inhibition of food intake. 10)Both metformin and pioglitazone are currently used as first-choice agents for the treatment for type 2 diabetes with obesity in Japan, even though they have opposite effects against body weight. Therefore it may be useful to clarify the differences in the effects of metformin and pioglitazone for prevention and treatment of obese type 2 diabetes and cardiovascular diseases produced as the result of development of metabolic syndrome. To investigate the effects of metformin on food intake and body weight gain, genetically obese diabetic mice such as db/db 11) or rats such as fa/fa, 12) GotoKakizaki (GK), 13) Otsuka Long-Evans Tokusima Fatty (OLETF), 14) and Zucker 15) have been generally used. However, daily oral administration of metformin to these genetically obese diabetic animals does not strongly affect body weight gain. On the other hand, we have recognized that daily treatment with pioglitazone given as food mixture (0.01, 0.02%) causes marked increases in food intake and body weight, although treatment with this drug removed hyperglycemia and hyperlipidemia. 16) Dietary fats are considered one of the most important environmental factors in the pathophysiology of obesity, and dietary fats-induced obesity is strongly related to lifestyle. However, it is unknown whether metformin causes body weight loss, while pioglitazone causes body weight gain, when administered to animals with high-fat diet-induced obes...

This study aimed to investigate the effects of a gamma-aminobutyric acid (GABA) rich tomato (Solanum lycopersicum L.) cultivar 'DG03-9' in comparison with 'Momotaro', a commonly consumed tomato cultivar in Japan, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). In a single administration study, treatment with the GABA-rich cultivar elicited a significant decrease in SBP compared to the control group. In a chronic administration study, SHR were fed diets containing one of the tomato cultivars for 4 weeks. Both cultivars significantly reduced the increase in SBP compared to the control. The antihypertensive effect of the GABA-rich cultivar was higher than that of the commonly consumed cultivar in both the single- and chronic-administration studies. Treatment with a comparable amount of GABA elicited a similar response to treatment with the GABA-rich cultivar. These results suggest that the GABA-rich cultivar 'DG03-9' is a potent antihypertensive food and may be useful for treating hypertension effectively.

Summary Enzymatically modified isoquercitrin (EMIQ) is a water-soluble glycoside of quercetin produced from rutin by enzymatic treatment. We investigated the anti-hypertensive effect of orally administered EMIQ in spontaneously hypertensive rats (SHR). The systolic blood pressure (SBP) in SHR administered EMIQ at a dose of 3 and 26 mg/kg/d was significantly lower than that in the control group on d 22, 36 and 50 of administration. The effect of EMIQ (26 mg/kg/d) was higher than equimolar administration of quercetin. Diltiazem administered as a positive control also suppressed the increase in SBP, and the effect was stronger than that of EMIQ. In the control group, the mean values of mean blood pressure (MBP) and diastolic blood pressure (DBP) were increased after the start of administration. Although diltiazem suppressed the increase in MBP, no significant changes were observed in the EMIQ groups. Compared with the control group, EMIQ groups showed the incidental changes of MBP and heart rate on day 22 of administration only. These results indicate that EMIQ suppressed the increase in SBP in SHR dose-dependently, and was more effective than the aglycone quercetin. It was also speculated that EMIQ showed higher antihypertensive effect than quercetin due to the high bioavailability, and the mechanism of SBP suppression is possibly through the improvement of endothelial NO production. In conclusion, our results suggest that EMIQ shows possibility as a naturally-derived safe food material which has an antihypertensive effect. Key Words enzymatically modified isoquercitrin, flavonoid, hypertension, blood pressure, spontaneously hypertensive rats Hypertension, which is closely related to the lifethreatening diseases arteriosclerosis and cardiovascular disease, is gathering increasing concern worldwide. There are many evidence-based antihypertensive medicines, such as calcium antagonist, angiotensin-converting enzyme (ACE) inhibitors and sympathetic blocking agents. However, with the recent increase of lifestylerelated diseases, there is growing concern about their prevention by dietary modification. There are many factors involved in hypertension, such as insufficient protein intake, excess intake of NaCl, and shortage of calcium and zinc, which are attributed to a disturbed nutritional status.Recently, oxidative stress due to reactive oxygen species (ROS), such as the superoxide radical and hydroxyl radical, has been reported to be involved in the development of hypertension ( 1 , 2 ). Negishi et al. reported an increase in the oxidative stress marker, urine 8-OHdG in a hypertensive patient compared with normotensive subjects suggesting that hypertensive patients have a high level of oxidative stress ( 3 ). Nitric oxide (NO) has a vasodepressor effect, and is closely related with oxidative stress ( 4 ). The increased ROS can decrease the halflife of NO. Certain reports suggested that the increase of ROS and simultaneous decrease of NO and antioxidants such as SOD and vitamin E occurs in essential hypertension ( 2 , 5...

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