Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM U1048), I2MC, CEDEX 4, 31432 Toulouse, France.
Université Paul Sabatier, I2MC-UPS, CHU Rangueil, CEDEX 4, 31432 Toulouse, France.
Molecules. 2021 Jun 23;26(13):3831. doi: 10.3390/molecules26133831.
Caffeine is a plant alkaloid present in food and beverages consumed worldwide. It has high lipid solubility with recognized actions in the central nervous system and in peripheral tissues, notably the adipose depots. However, the literature is scant regarding caffeine's influence on adipocyte functions other than lipolysis, such as glucose incorporation into lipids (lipogenesis) and amine oxidation. The objective of this study was to explore the direct effects of caffeine and of isobutylmethylxanthine (IBMX) on these adipocyte functions. Glucose transport into fat cells freshly isolated from mice, rats, or humans was monitored by determining [H]-2-deoxyglucose (2-DG) uptake, while the incorporation of radiolabeled glucose into cell lipids was used as an index of lipogenic activity. Oxidation of benzylamine by primary amine oxidase (PrAO) was inhibited by increasing doses of caffeine in human adipose tissue preparations with an inhibition constant (Ki) in the millimolar range. Caffeine inhibited basal and insulin-stimulated glucose transport as well as lipogenesis in rodent adipose cells. The antilipogenic action of caffeine was also observed in adipocytes from mice genetically invalidated for PrAO activity, indicating that PrAO activity was not required for lipogenesis inhibition. These caffeine inhibitory properties were extended to human adipocytes: relative to basal 2-DG uptake, set at 1.0 ± 0.2 for 6 individuals, 0.1 mM caffeine tended to reduce uptake to 0.83 ± 0.08. Insulin increased uptake by 3.86 ± 1.11 fold when tested alone at 100 nM, and by 3.21 ± 0.80 when combined with caffeine. Our results reinforce the recommendation of caffeine's potential in the treatment or prevention of obesity complications.
咖啡因是一种存在于世界各地食用和饮用的食品和饮料中的植物生物碱。它具有很高的脂溶性，在中枢神经系统和外周组织中具有公认的作用，特别是脂肪组织。然而，关于咖啡因对脂肪细胞功能的影响，除了脂肪分解外，如葡萄糖掺入脂质（脂肪生成）和胺氧化，文献很少。本研究的目的是探讨咖啡因和异丁基甲基黄嘌呤（IBMX）对这些脂肪细胞功能的直接影响。通过测定[H]-2-脱氧葡萄糖（2-DG）摄取来监测从小鼠、大鼠或人类新鲜分离的脂肪细胞中葡萄糖的转运，而放射性标记的葡萄糖掺入细胞脂质则用作脂肪生成活性的指标。在人脂肪组织制剂中，随着咖啡因剂量的增加，苯甲胺氧化酶（PrAO）的苄胺氧化被抑制，抑制常数（Ki）在毫摩尔范围内。咖啡因抑制啮齿动物脂肪细胞的基础和胰岛素刺激的葡萄糖转运以及脂肪生成。在 PrAO 活性遗传无效的小鼠脂肪细胞中也观察到咖啡因的抗脂肪生成作用，表明 PrAO 活性不是脂肪生成抑制所必需的。这些咖啡因抑制特性也扩展到人类脂肪细胞：与 6 个人的基础 2-DG 摄取（设定为 1.0 ± 0.2）相比，0.1 mM 咖啡因倾向于将摄取量降低至 0.83 ± 0.08。当单独测试时，胰岛素将摄取量增加了 3.86 ± 1.11 倍，当与咖啡因结合时，胰岛素将摄取量增加了 3.21 ± 0.80 倍。我们的结果强化了咖啡因在肥胖并发症的治疗或预防中的潜在应用的建议。
