INSERM, U, Le Kremlin-Bicêtre, France.
Br J Pharmacol. 2013 Jan;168(1):139-50. doi: 10.1111/j.1476-5381.2012.02140.x.
Carbamazepine (CBZ), known for its anti-epileptic, analgesic and mood-stabilizing properties, is also known to induce weight gain but the pathophysiology of this adverse effect is still largely unknown. We tested the hypothesis that CBZ could have a direct effect on adipocyte development and metabolism. EXPERIMENTAL RESEARCH: We studied the effects of CBZ on morphological biochemical and molecular markers of adipogenesis, using several pre-adipocyte murine cell lines (3T3-L1, 3T3-F442A and T37i cells) and primary cultures of human pre-adipocytes. To delineate the mechanisms underlying the effect of CBZ, clonal expansion of pre-adipocytes, pro-adipogenic transcription factors, glucose uptake and lipolysis were also examined.
CBZ strongly inhibited pre-adipocyte differentiation and triglyceride accumulation in a time- and dose-dependent manner in all models. Pleiotropic mechanisms were at the basis of the inhibitory effects of CBZ on adipogenesis and cell lipid accumulation. They included suppression of both clonal expansion and major adipogenic transcription factors such as PPAR-γ and CCAAT/enhancer binding protein-α, activation of basal lipolysis and decrease in insulin-stimulated glucose transport.
The effect of CBZ on adipogenesis involves activation of the ERK1/2 pathway. Our results show that CBZ acts directly on pre-adipocytes and adipocytes to alter adipose tissue development and metabolism.
卡马西平（CBZ）具有抗癫痫、镇痛和稳定情绪的特性，也被认为会导致体重增加，但这种不良反应的病理生理学机制仍知之甚少。我们检验了 CBZ 可能对脂肪细胞发育和代谢有直接影响的假说。
我们使用几种前体脂肪细胞鼠细胞系（3T3-L1、3T3-F442A 和 T37i 细胞）和原代培养的人类前体脂肪细胞，研究了 CBZ 对脂肪生成的形态、生化和分子标志物的影响。为了阐明 CBZ 作用的机制，我们还检查了前体脂肪细胞的克隆扩增、前脂肪生成转录因子、葡萄糖摄取和脂肪分解。
CBZ 在所有模型中均以时间和剂量依赖的方式强烈抑制前体脂肪细胞分化和甘油三酯积累。CBZ 对脂肪生成和细胞脂质积累的抑制作用的基础是多效性机制。它们包括抑制克隆扩增和主要脂肪生成转录因子（如 PPAR-γ 和 CCAAT/增强子结合蛋白-α）、激活基础脂肪分解和减少胰岛素刺激的葡萄糖转运。
CBZ 对脂肪生成的作用涉及 ERK1/2 途径的激活。我们的结果表明，CBZ 直接作用于前体脂肪细胞和脂肪细胞，改变脂肪组织的发育和代谢。
