Richard D, Picard F, Lemieux C, Lalonde J, Samson P, Deshaies Y
Centre de recherche de l'Hôpital Laval et Centre de recherche sur le métabolisme énergétique de l'Université Laval, Québec, Canada.
Int J Obes Relat Metab Disord. 2002 Mar;26(3):344-53. doi: 10.1038/sj.ijo.0801873.
The effects of topiramate (TPM) on components of energy balance were tested in male and female rats that were (i) left intact, (ii) castrated or (iii) castrated with replacement therapies consisting of testosterone administration in orchidectomized (OCX) rats and of estradiol or progesterone treatments in ovariectomized (OVX) rats.
TPM was mixed into the diet and administered at a dose of 60 mg per kg of body weight. Male and female rats were treated for 28 and 35 days, respectively. At the end of the treatment period, variables of energy balance and determinants of lipid and glucose metabolism were assessed.
TPM reduced energy and fat gains in both male and female rats either in the absence or in the presence of hormone replacement therapies. In male rats, it also decreased food intake, protein gain and energetic efficiency. In female animals, TPM reduced energetic efficiency while it stimulated lipoprotein lipase activity in brown adipose tissue. TPM also reduced plasma glucose and plasma leptin levels in female rats as well as plasma insulin and liver triglycerides in male animals. As expected, castration and sex hormones also strongly influenced energy balance. In male rats, OCX led to a decrease in energy and protein gains that was blocked by treatment with testosterone. In female rats, OVX caused increases in energy, fat and protein gains that were prevented by treatment with estradiol.
In female rats, the effects of TPM on fat and energy gains were clearly not influenced by the sex hormone status of the rats. In male animals, there was also no interaction of TPM and the status of sex hormones on energy balance, suggesting that OCX and testosterone minimally interfere with the action of TPM on energy balance. The effects of TPM on energy balance were accounted for by a decrease in energetic efficiency, resulting from an effect exerted by the drug on both energy intake and thermogenesis. The present results also suggest that TPM can enhance insulin sensitivity.
在雄性和雌性大鼠中测试托吡酯（TPM）对能量平衡各组成部分的影响，这些大鼠分为以下三组：（i）未处理组；（ii）去势组；（iii）去势后接受替代疗法组，即对去势雄鼠给予睾酮，对去势雌鼠给予雌二醇或孕酮治疗。
将TPM混入饲料中，以每千克体重60毫克的剂量给药。雄性和雌性大鼠分别接受28天和35天的治疗。在治疗期结束时，评估能量平衡变量以及脂质和葡萄糖代谢的决定因素。
无论是否存在激素替代疗法，TPM均能减少雄性和雌性大鼠的能量和脂肪增加。在雄性大鼠中，TPM还能减少食物摄入量、蛋白质增加量和能量效率。在雌性动物中，TPM降低了能量效率，同时刺激了棕色脂肪组织中的脂蛋白脂肪酶活性。TPM还降低了雌性大鼠的血浆葡萄糖和血浆瘦素水平，以及雄性动物的血浆胰岛素和肝脏甘油三酯水平。正如预期的那样，去势和性激素也强烈影响能量平衡。在雄性大鼠中，去势导致能量和蛋白质增加量减少，而睾酮治疗可阻止这种减少。在雌性大鼠中，去势导致能量、脂肪和蛋白质增加量增加，而雌二醇治疗可防止这种增加。
在雌性大鼠中，TPM对脂肪和能量增加的影响显然不受大鼠性激素状态的影响。在雄性动物中，TPM与性激素状态对能量平衡也没有相互作用性，这表明去势和睾酮对TPM在能量平衡方面的作用干扰极小。TPM对能量平衡的影响是由能量效率降低所致，这是该药物对能量摄入和产热均产生作用的结果。目前的结果还表明，TPM可增强胰岛素敏感性。
