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首页> 外文期刊>American Journal of Physiology >CB1 receptor antagonist AVE1625 affects primarily metabolic parameters independently of reduced food intake in Wistar rats.
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CB1 receptor antagonist AVE1625 affects primarily metabolic parameters independently of reduced food intake in Wistar rats.

机译：CB1受体拮抗剂AVE1625主要影响代谢参数，与Wistar大鼠食物摄入减少无关。

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The objective of the present study was to investigate in fed Wistar rats whether the cannabinoid-1 (CB1) receptor antagonist AVE1625 causes primary effects on metabolic blood and tissue parameters as well as metabolic rate, which are independent of reduced caloric intake. After single administration to rats postprandially, AVE1625 caused a slight dose-dependent increase in basal lipolysis. Six hours after single administration, liver glycogen content was dose-dependently reduced to approximately 60% of that of untreated controls. These findings demonstrate a primary acute effect of AVE1625 on induction of 1) lipolysis from fat tissue (increased FFA) and 2) glycogenolysis from the liver (reduced hepatic glycogen). Measured by indirect calorimetry, AVE1625 caused an immediate increase in total energy expenditure, a long-lasting increase of fat oxidation, and a transient increase of glucose oxidation, which were consistent with the acute findings on metabolic blood and tissue parameters. We conclude that,in addition to the well-investigated effects of CB1 receptor antagonists to reduce caloric intake and subsequently body weight, this pharmacological approach is additionally linked to inherently increased lipid oxidation. This oxidation is driven by persistently increased lipolysis from fat tissues, independently of reduced caloric intake, and might significantly contribute to the weight-reducing effect.
机译：本研究的目的是研究进食Wistar大鼠时，大麻素1（CB1）受体拮抗剂AVE1625是否对代谢血液和组织参数以及代谢率产生主要影响，而这些影响与降低热量摄入无关。餐后对大鼠单次给药后，AVE1625引起基础脂解的剂量依赖性增加。单次给药后六小时，肝糖原含量呈剂量依赖性降低至未处理对照组的约60％。这些发现证明了AVE1625对1）诱导脂肪组织脂解（FFA增加）和2）肝糖原分解（肝糖原减少）的主要急性作用。通过间接量热法测量，AVE1625导致总能量消耗立即增加，脂肪氧化持久增加和葡萄糖氧化短暂增加，这与代谢性血液和组织参数的急性发现一致。我们得出的结论是，除了对CB1受体拮抗剂减少热量摄入和随后减轻体重的充分研究效果外，这种药理学方法还与脂质氧化固有地增加有关。这种氧化是由脂肪组织持续增加的脂解作用所驱动的，与热量的摄入减少无关，并且可能显着地减轻了体重。

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