Gallardo Nilda, Bonzón-Kulichenko Elena, Fernández-Agulló Teresa, Moltó Eduardo, Gómez-Alonso Sergio, Blanco Pablo, Carrascosa Jose Maria, Ros Manuel, Andrés Antonio
Area de Bioquímica, Facultad de Químicas, Regional Centre for Biomedical Research, Avenida Camilo José Cela 10, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
Endocrinology. 2007 Dec;148(12):5604-10. doi: 10.1210/en.2007-0933. Epub 2007 Sep 6.
Leptin reduces adiposity and exerts antisteatotic effects on nonadipose tissues. However, the mechanisms underlying leptin effects on lipid metabolism in liver and white adipose tissue have not been fully clarified. Here, we have studied the effects of central leptin administration on key enzymes and transcription factors involved in lipid metabolism in liver and epididymal adipose tissue. Intracerebroventricular leptin infusion for 7 d did not change leptin plasma levels but decreased triacylglyceride content in liver, epididymal adipose tissue, and plasma. In both tissues this treatment markedly decreased the expression of key enzymes of the de novo fatty acid (FA) synthesis such as acetyl-coenzyme A-carboxylase, FA synthase, and stearoyl-coenzyme A desaturase-1, in parallel with a reduction in mRNA expression of sterol regulatory element binding protein-1c in liver and carbohydrate regulatory element binding protein in adipose tissue. In addition, leptin also decreased phosphoenol-pyruvate carboxykinase-C expression in adipose tissue, an enzyme involved in glyceroneogenesis in this tissue. Central leptin administration down-regulates delta-6-desaturase expression in liver and adipose tissue, in parallel with the decrease of the expression of sterol regulatory element binding protein-1c in liver and peroxisome proliferator activated receptor alpha in adipose tissue. Finally, leptin treatment, by regulating adipose triglyceride lipase/hormone sensitive lipase/diacylglycerol transferase 1 expression, also established a new partitioning in the FA-triacylglyceride cycling in adipose tissue, increasing lipolysis and probably the FA efflux from this tissue, and favoring in parallel the FA uptake and oxidation in the liver. These results suggest that leptin, acting at central level, exerts tissue-specific effects in limiting fat tissue mass and lipid accumulation in nonadipose tissues, preventing the development of obesity and type 2 diabetes.
瘦素可减少肥胖，并对非脂肪组织发挥抗脂肪变性作用。然而，瘦素对肝脏和白色脂肪组织脂质代谢影响的潜在机制尚未完全阐明。在此，我们研究了中枢给予瘦素对肝脏和附睾脂肪组织中参与脂质代谢的关键酶和转录因子的影响。脑室内注入瘦素7天未改变血浆瘦素水平，但降低了肝脏、附睾脂肪组织和血浆中的甘油三酯含量。在这两种组织中，该处理均显著降低了从头脂肪酸（FA）合成关键酶的表达，如乙酰辅酶A羧化酶、FA合酶和硬脂酰辅酶A去饱和酶-1，同时肝脏中固醇调节元件结合蛋白-1c和脂肪组织中碳水化合物调节元件结合蛋白的mRNA表达也降低。此外，瘦素还降低了脂肪组织中磷酸烯醇丙酮酸羧激酶-C的表达，该酶参与该组织中的甘油生成。中枢给予瘦素可下调肝脏和脂肪组织中δ-6-去饱和酶的表达，同时降低肝脏中固醇调节元件结合蛋白-1c和脂肪组织中过氧化物酶体增殖物激活受体α的表达。最后，瘦素处理通过调节脂肪甘油三酯脂肪酶/激素敏感性脂肪酶/二酰甘油转移酶1的表达，还在脂肪组织的FA-甘油三酯循环中建立了新的分配方式，增加了脂肪分解，可能还增加了该组织中FA的流出，并同时促进了肝脏中FA的摄取和氧化。这些结果表明，瘦素在中枢水平发挥作用，在限制脂肪组织量和非脂肪组织脂质积累方面发挥组织特异性作用，预防肥胖和2型糖尿病的发生。
