González-Yanes C, Sánchez-Margalet V
Department of Medical Biochemistry and Molecular Biology, School of Medicine, Investigation Unit, Virgen Macarena University Hospital, Av. Sanchez Pizjuan 4, Seville 41009, Spain.
Cell Mol Life Sci. 2003 Dec;60(12):2749-56. doi: 10.1007/s00018-003-3346-7.
Leptin, the ob gene product, is an adipocyte-secreted hormone that centrally regulates weight by decreasing caloric intake and increasing energy expenditure. Expression of leptin is regulated by dietary status, insulin, glucocorticoids and catecholamines. Pancreastatin (PST), a chromogranin A-derived peptide, correlates with catecholamine levels, and may play a role in the physiology of stress, modulating endocrine secretion and metabolism. Thus, PST has been found to exert a lipolytic and anti-insulin effect in white adipocytes. The aim of the present work was to investigate a possible role of PST modulating the expression of key genes involved in lipid storage and metabolism: leptin, PPAR-gamma2, UCP-1 and UCP-2. We incubated isolated rat epididymal adipocytes with 100 nM PST for 16 and 24 h. Leptin, UCP-2 and UCP-1 mRNA levels were assessed by RT-PCR, followed by Southern blot. Leptin secretion was also measured by ELISA. PST inhibited leptin expression and secretion at 16-h incubation, but this effect was no longer observed after 24 h. On the other hand, PST stimulated the expression of UCP-2 after 16 h. However, the effect was still significant after 24 h. The inhibitory effect of PST on leptin expression and secretion and the stimulation of UCP-2 expression were prevented by blocking PKC. UCP-1 and PPR-gamma2 expression did not change after PST stimulation. Leptin differentially regulates the expression of key genes in the rat adipocyte, upregulating the expression of UCP-2 and inhibiting the expression and secretion of leptin by a mechanism that involves PKC activity. These effects may contribute to the metabolic action of catecholamines in physiological and pathophysiological conditions with increased sympathetic activity.
瘦素是肥胖（ob）基因的产物，是一种由脂肪细胞分泌的激素，通过减少热量摄入和增加能量消耗来调节体重。瘦素的表达受饮食状态、胰岛素、糖皮质激素和儿茶酚胺的调控。胰抑制素（PST）是一种源自嗜铬粒蛋白A的肽，与儿茶酚胺水平相关，可能在应激生理过程中发挥作用，调节内分泌分泌和代谢。因此，已发现PST在白色脂肪细胞中具有脂解和抗胰岛素作用。本研究的目的是探讨PST调节参与脂质储存和代谢的关键基因表达的可能作用：瘦素、过氧化物酶体增殖物激活受体γ2（PPAR-γ2）、解偶联蛋白1（UCP-1）和解偶联蛋白2（UCP-2）。我们将分离的大鼠附睾脂肪细胞与100 nM PST孵育16小时和24小时。通过逆转录聚合酶链反应（RT-PCR）评估瘦素、UCP-2和UCP-1的mRNA水平，随后进行Southern印迹分析。瘦素分泌也通过酶联免疫吸附测定（ELISA）进行测量。在孵育16小时时，PST抑制瘦素的表达和分泌，但在24小时后不再观察到这种效应。另一方面，PST在16小时后刺激UCP-2的表达。然而，在24小时后该效应仍然显著。通过阻断蛋白激酶C（PKC）可防止PST对瘦素表达和分泌的抑制作用以及对UCP-2表达的刺激作用。PST刺激后，UCP-1和PPAR-γ2的表达没有变化。瘦素以一种涉及PKC活性的机制差异调节大鼠脂肪细胞中关键基因的表达，上调UCP-2的表达并抑制瘦素的表达和分泌。这些效应可能有助于儿茶酚胺在交感神经活动增加的生理和病理生理条件下的代谢作用。
