Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
PLoS One. 2011;6(9):e25565. doi: 10.1371/journal.pone.0025565. Epub 2011 Sep 27.
Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid β-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes.
除了在分娩和哺乳期间发挥作用外，催产素还参与了其他几种功能。有趣的是，催产素和催产素受体缺失的小鼠在正常饮食摄入的情况下发展为迟发性肥胖，这表明该激素可能发挥一系列有益的代谢作用。最近的数据证实了这一点，这些数据表明，中枢催产素输注可导致饮食诱导肥胖小鼠体重减轻。本研究的目的是揭示催产素产生这种有益作用的机制。在高脂肪饮食诱导肥胖大鼠中进行了慢性中枢催产素输注。测定其对体重、脂代谢和胰岛素敏感性的影响。我们观察到体重增加呈剂量依赖性下降，脂肪组织脂解和脂肪酸β氧化增加，以及葡萄糖耐量和胰岛素抵抗降低。中枢输注后血浆催产素水平升高的额外观察结果表明，该激素可能通过直接作用影响脂肪组织代谢。这通过体外、离体和体内实验得到了证明。关于其在脂肪组织中的作用机制，催产素增加了硬脂酰辅酶 A 去饱和酶 1 的表达，以及磷脂前体 N-油酰-磷酸乙醇胺的组织含量，N-油酰-磷酸乙醇胺是油酸衍生的 PPAR-α激活剂，油酰乙醇酰胺的生物合成前体。由于 PPAR-α 调节脂肪酸β氧化，我们假设该转录因子可能介导催产素的作用。这一假设得到了以下观察结果的证实：与在野生型小鼠中的作用相反，在 PPAR-α 缺失动物中，催产素输注未能诱导体重减轻和脂肪氧化。总而言之，这些结果表明，催产素给药可能代表治疗人类肥胖和 2 型糖尿病的一种有前途的治疗方法。
