(57/472) Anti-obesity effects of chikusetsusaponins isolated from Panax japonicus rhizomes.
BACKGROUND: The rhizomes of Panax japonicus are used as a folk medicine for treatment of life-style related diseases such as arteriosclerosis, hyperlipidemia, hypertension and non-insulin-dependent diabetes mellitus as a substitute for ginseng roots in China and Japan. Obesity is closely associated with life-style-related diseases. This study was performed to clarify whether chikusetsusaponins prevent obesity induced in mice by a high-fat diet for 9 weeks. METHODS: We performed two in vivo experiments. In one, female ICR mice were fed a high-fat diet with or without 1 or 3% chikusetsusaponins isolated from P. japonicus rhizomes for 9 weeks. In the other, lipid emulsion with or without chikusetsusaponins was administered orally to male Wistar rats, and then the plasma triacylglycerol level was measured 0.5 to 5 h after the orally administered lipid emulsion. For in vitro experiments, the inhibitory effects of total chikusetsusaponins and various purified chikusetsusaponins on pancreatic lipase activity were determined by measuring the rate of release of oleic acid from triolein in an assay system using triolein emulsified with lecithin. RESULTS: Total chikusetsusaponins prevented the increases in body weight and parametrial adipose tissue weight induced by a high-fat diet. Furthermore, consumption of a high-fat diet containing 1 or 3% total chikusetsusaponins significantly increased the fecal content and triacylglycerol level at day 3 compared with the high-fat diet groups. Total chikusetsusaponins inhibited the elevation of the plasma triacylglycerol level 2 h after the oral administration of the lipid emulsion. Total chikusetsusaponins, chikusetsusaponin III, 28-deglucosyl-chikusetsusaponin IV and 28-deglucosyl-chikusetsusaponin V inhibited the pancreatic lipase activity. CONCLUSION: The anti-obesity effects of chikusetsusaponins isolated from P. japonicus rhizomes in mice fed a high-fat diet may be partly mediated through delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity. The present study clearly indicated that the saponin fractions of P. japonicus rhizomes had a significant anti-obesity action and supports the traditional usage as a substitute drug for ginseng roots. (+info)
(58/472) Add-on topiramate reduces weight in overweight patients with affective disorders: a clinical case series.
BACKGROUND: The weight-gain caused by many psychotropic drugs is a major cause for poor compliance with such medications and could also increase cardio-vascular morbidity among psychiatric patients. Recent reports have shown that the anticonvulsant topiramate causes weight loss in various patient groups. The drug has also shown effectiveness in open trials as a mood stabilizer in patients with affective disorders, but not in controlled trials in the acute treatment of mania. We used topiramate to treat 12 patients with affective disorders who had a body-mass index > 30 kg/m2. METHODS: Topiramate was prescribed as part of our routine clinical practice, as an add-on medication, or as a replacement of a mood stabilizer. Patients' weight was recorded in 1 to 2 monthly intervals. Patients were followed up for between 6 and 12 months. The final dose of topiramate varied from 200 to 600 mg/day. RESULTS: Topiramate was effective in reducing the weight in 10 out of the 12 patients. At six months the 12 patients had lost a mean of 7.75 kg (SD = 6.9 kg, p < 0.001) and at 12 months 9 patients had lost a mean of 9.61 kg (SD = 6.7 kg, p = 0.003). Three patients stopped the treatment: one due to side effects, one due to possible side effects, and one suffered a manic relapse and showed no sustained weight loss. There were no other clear changes in the course of illness of the patients. CONCLUSION: The evidence of a strong weight-reducing potential of topiramate is indisputable and clinically significant. Topiramate could be considered in the treatment of bipolar patients who are overweight, or whose concerns about weight gain compromise their compliance with long-term prophylactic medication. So far there is no evidence that topiramate has anti-manic effect and it should not be used as monotherapy. (+info)
(59/472) Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene.
BACKGROUND: Orlistat (Xenicaltrade mark), a US Food and Drug Administration (FDA)-approved drug for bodyweight loss, has recently been demonstrated to exhibit antitumor properties towards prostate cancer cells by virtue of its ability to block the lipogenic activity of fatty acid synthase (FAS). FAS (oncogenic antigen-519) is up-regulated in about 50% of breast cancers, is an indicator of poor prognosis, and has recently been functionally associated with the Her2/neu (erbB-2) oncogene. MATERIALS AND METHODS: We assessed the antitumoral effects of orlistat against the human breast cancer cell line SK-Br3, an in vitro paradigm of FAS and Her2/neu overexpression in breast cancer. RESULTS: Cell cycle analyses revealed that micromolar concentrations of orlistat induced, in a time- and dose-dependent manner, significant changes in the distribution of cell populations including a complete loss of G2-M phase, S-phase accumulation and a concomitant increase in the emerging sub-G1 (apoptotic) cells. Poly (ADP-ribose) polymerase (PARP) cleavage, an early event required for cells committed to apoptosis, was more predominant in orlistat-treated G1 phase cells. When we characterized signaling molecules participating in the cellular events following orlistat-induced inhibition of FAS activity and preceded inhibition of breast cancer cell proliferation, a dramatic down-regulation of Her2/neu-coded p185(Her2/neu) oncoprotein was found in orlistat-treated SK-Br3 cells (>90% reduction). Interestingly, a significant accumulation of the DNA-binding protein PEA3, a member of the Ets transcription factor family that specifically targets a PEA3-binding motif present on the Her2/neu gene promoter and down-regulates its activity, was observed in orlistat-treated SK-Br3 cells. When a Luciferase reporter gene driven by the Her2/neu promoter was transiently transfected in SK-Br3 cells, orlistat exposure was found to dramatically repress the promoter activity of Her2/neu gene, whereas a Her2/neu promoter bearing a mutated binding DNA sequence was not subject to negative regulation by orlistat, thus demonstrating that the intact PEA3 binding site on the Her2/neu promoter is required for the orlistat-induced transcriptional repression of Her2/neu overexpression. RNA interference (RNAi)-mediated silencing of FAS gene expression similarly repressed Her2/neu gene expression in a PEA3-dependent manner, thus ruling out a role for non-FAS orlistat-mediated effects. When the combination of orlistat and the anti-Her2/neu antibody trastuzumab (Herceptintrade mark) in either concurrent (orlistat + trastuzumab) or sequential (orlistat --> trastuzumab; trastuzumab --> orlistat) schedules was tested for synergism, addition or antagonism using the combination index (CI) method of Chou-Talalay, co-exposure of orlistat and trastuzumab demonstrated strong synergistic effects (CI10-90 = 0.110-0.847), whereas sequential exposure to orlistat followed by trastuzumab (CI10-90 = 0.380-1.210) and trastuzumab followed by orlistat (CI10-90 = 0.605-1.278) mainly showed additive or antagonistic interactions. Indeed, orlistat-induced FAS inhibition synergistically promoted apoptotic cell death when concurrently combined with trastuzumab as determined by an ELISA for histone-associated DNA fragments. Importantly, the degree of FAS expression in a panel of human breast cancer cell lines was predictive of sensitivity to orlistat-induced anti-proliferative effects as determined by a MTT-based characterization of metabolically viable breast cancer cells. Moreover, hypersensitivity to orlistat-induced cytotoxicity was observed in MCF-7 breast cancer cells engineered to overexpress Her2/neu (MCF-7/Her2-18 cells), which exhibit a significant up-regulation of FAS expression and activity. CONCLUSIONS: These findings reveal that the development of more potent and/or bioavailable orlistat's variants targeting the lipogenic activity of FAS may open a novel therapeutic avenue for treating Her2/neu-overexpressing breast carcinomas. (+info)
(60/472) Dietary gallate esters of tea catechins reduce deposition of visceral fat, hepatic triacylglycerol, and activities of hepatic enzymes related to fatty acid synthesis in rats.
Tea catechins, rich in (-)-epigallocatechin gallate and (-)-epicatechin gallate, or heat-treated tea catechins in which about 50% of the (-)-epigallocatechin gallate and (-)-epicatechin gallate in tea catechins was epimerized to (-)-gallocatechin gallate and (-)-catechin gallate, were fed to rats at 1% level for 23 d. Visceral fat deposition and the concentration of hepatic triacylglycerol were significantly lower in the tea catechin and heat-treated tea catechin groups than in the control group. The activities of fatty acid synthase and the malic enzyme in the liver cytosol were significantly lower in the two catechin groups than in the control group. In contrast, the activities of carnitine palmitoyltransferase and acyl-CoA oxidase in the liver homogenate were not significantly different among the three groups. These results suggest that the reduction in activities of enzymes related to hepatic fatty acid synthesis by the feeding of tea catechins or heat-treated tea catechins can cause reductions of hepatic triacylglycerol and possibly of visceral fat deposition. (+info)
(61/472) The effect of Irvingia gabonensis seeds on body weight and blood lipids of obese subjects in Cameroon.
Dietary fibres are frequently used for the treatment of obesity. The aim of this study was to evaluate the efficacy of Irvingia gabonensis seeds in the management of obesity. This was carried out as a double blind randomised study involving 40 subjects (mean age 42.4 years). Twenty-eight subjects received Irvingia gabonensis (IG) (1.05 g three time a day for one month) while 12 were on placebo (P) and the same schedule. During the one-month study period all subjects were on a normocaloric diet evaluated every week by a dietetic record book. At the end, the mean body weight of the IG group was decreased by 5.26 +/- 2.37% (p < 0.0001) and that of the placebo group by 1.32 +/- 0.41% (p < 0.02). The difference observed between the IG and the placebo groups was significant (p < 0.01). The obese patients under Irvingia gabonensis treatment also had a significant decrease of total cholesterol, LDL-cholesterol, triglycerides, and an increase of HDL-cholesterol. On the other hand, the placebo group did not manifest any changes in blood lipid components. Irvingia gabonensis seed may find application in weight lose. (+info)
(62/472) Effects of fenugreek seed extract in obese mice fed a high-fat diet.
It was found that fenugreek seed extract reduced the body weight gain induced by a high-fat diet in obese mice. The extract decreased plasma triglyceride gain induced by oil administration. The major component of the extract, 4-hydroxyisoleucine, also decreased plasma triglyceride gain. Consequently, fenugreek seed extract is expected to prevent the obesity induced by a high-fat diet. (+info)
(63/472) Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats.
BACKGROUND AND AIMS: Ghrelin, the natural ligand of the growth hormone secretagogue receptor 1a, is the most powerful peripherally active orexigenic agent known. In rodents, ghrelin administration stimulates growth hormone release, food intake, and adiposity. Because of these effects, blocking of ghrelin has been widely discussed as a potential treatment for obesity. Spiegelmer NOX-B11 is a synthetic l-oligonucleotide, which was previously shown to bind ghrelin. We examined the effects of NOX-B11 on ghrelin induced neuronal activation and food intake in non-fasted rats. METHODS: Animals received various doses of NOX-B11, inactive control Spiegelmer, or vehicle intravenously. Ghrelin or vehicle was administered intraperitoneally 12 hours later and food intake was measured over four hours. Neuronal activation was assessed as c-Fos-like immunoreactivity in the arcuate nucleus. RESULTS: Treatment with NOX-B11 30 nmol suppressed ghrelin induced c-Fos-like immunoreactivity in the arcuate nucleus and blocked the ghrelin induced increase in food intake within the first half hour after ghrelin injection (mean 1.13 (SEM 0.59) g/kg body weight; 4.94 (0.63) g/kg body weight versus 0.58 (0.58) g/kg body weight; p<0.0001). Treatment with NOX-B11 1 nmol or control Spiegelmer had no effect whereas treatment with NOX-B11 10 nmol showed an intermediate effect on ghrelin induced food intake. CONCLUSIONS: Spiegelmer NOX-B11 suppresses ghrelin induced food intake and c-Fos induction in the arcuate nucleus in rats. The use of an anti-ghrelin Spiegelmer could be an innovative new approach to inhibit the biological action of circulating ghrelin. This may be of particular relevance to conditions associated with elevated plasma ghrelin, such as the Prader-Willi syndrome. (+info)
(64/472) Exercise training as an adjunct to orlistat therapy reduces oxidative stress in obese subjects.
The anti-obesity drug orlistat promotes weight loss and improves obesity-related risk factors, but its effect on oxidative stress is not clear yet. Orlistat reduces dietary fat absorption, which may have effects on fat soluble vitamins especially the antioxidant vitamins A and E. The aim of this study was to determine and compare the effects of weight loss achieved by orlistat therapy and a combination of orlistat with aerobic exercise training on lipid peroxidation and antioxidative defense in obese subjects. Total of 24 obese subjects were randomly assigned to receive 12-week treatment with hypocaloric diet-orlistat (120 mg three times daily) (DO group) or diet-orlistat-exercise (DOE group). Serum levels of malondialdehyde (MDA), a marker for lipid peroxidation, and vitamins A and E were measured by high performance liquid chromatography at baseline and at the end of the treatment. Body weight and fat mass were significantly reduced in the two groups (p < 0.001). In the DO group, the MDA levels remained unchanged (p = 0.59), while vitamins A (p < 0.01) and E (p < 0.001) were significantly decreased. In contrast, the subjects treated with DOE exhibited marked decreases in MDA (p = 0.002) and a small but significant decrease in vitamins A (p = 0.003) and E (p = 0.003). Thus, orlistat therapy alone caused a significant reduction in antioxidative capacity without affecting oxidative stress, whereas orlistat in combination with exercise training provided a significant decrease in MDA levels. The beneficial effect of aerobic exercise as an adjunct to the orlistat therapy is of importance with regard to the obesity-associated risk factors. (+info)