Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, Spain.
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain.
Cells. 2021 Mar 6;10(3):581. doi: 10.3390/cells10030581.
Central actions of leptin and insulin on hepatic lipid metabolism can be opposing and the mechanism underlying this phenomenon remains unclear. Both hormones can modulate the central somatostatinergic system that has an inhibitory effect on growth hormone (GH) expression, which plays an important role in hepatic metabolism. Using a model of chronic central leptin infusion, we evaluated whether an increase in central leptin bioavailability modifies the serum lipid pattern through changes in hepatic lipid metabolism in male rats in response to an increase in central insulin and the possible involvement of the GH axis in these effects. We found a rise in serum GH in leptin plus insulin-treated rats, due to an increase in pituitary GH mRNA levels associated with lower hypothalamic somatostatin and pituitary somatostatin receptor-2 mRNA levels. An augment in hepatic lipolysis and a reduction in serum levels of non-esterified fatty acids (NEFA) and triglycerides were found in leptin-treated rats. These rats experienced a rise in lipogenic-related factors and normalization of serum levels of NEFA and triglycerides after insulin treatment. These results suggest that an increase in insulin in leptin-treated rats can act on the hepatic lipid metabolism through activation of the GH axis.
瘦素和胰岛素对肝脏脂质代谢的中枢作用可能是相反的，而这种现象的机制尚不清楚。这两种激素都可以调节中枢生长抑素能系统，该系统对生长激素 (GH) 的表达具有抑制作用，GH 在肝脏代谢中起着重要作用。使用慢性中枢性瘦素输注模型，我们评估了在雄性大鼠中，中枢性瘦素生物利用度的增加是否通过改变肝脏脂质代谢来改变血清脂质谱，以响应中枢性胰岛素的增加，以及 GH 轴在这些影响中的可能参与。我们发现，由于与下丘脑中生长抑素和垂体生长抑素受体 2 mRNA 水平降低相关的垂体 GH mRNA 水平增加，在瘦素加胰岛素处理的大鼠中血清 GH 升高。在瘦素处理的大鼠中，发现肝脂肪分解增加，血清中非酯化脂肪酸 (NEFA) 和甘油三酯水平降低。这些大鼠在胰岛素治疗后经历了与脂肪生成相关的因素增加和血清 NEFA 和甘油三酯水平的正常化。这些结果表明，在瘦素处理的大鼠中，胰岛素的增加可以通过激活 GH 轴来作用于肝脏脂质代谢。
