Regulation of the enzymes of hepatic microsomal triacylglycerol lipolysis and re-esterification by the glucocorticoid dexamethasone
Regulation of the enzymes of hepatic microsomal triacylglycerol lipolysis and re-esterification by the glucocorticoid dexamethasone
复制标题
DOI：
10.1042/bj20031320
复制
发表时间：
2004-03-15
影响因子：
4.1
通讯作者：
Vance, DE
中科院分区：
文献类型：
--
作者：
Dolinsky, VW;Douglas, DN;Vance, DE
肝脏VLDL（极低密度脂蛋白）组装是一个复杂的过程，主要受载脂蛋白B组装所需的脂质调节。细胞内储存的TAG（三酰基甘油）经历最初的脂解，随后脂解产物再酯化形成TAG，然后将其并入VLDL颗粒。TGH （TAG水解酶）是一种在肝细胞内水解TAG的脂肪酶。我们利用注射地塞米松的小鼠和原代肝细胞模型来研究合成糖皮质激素、地塞米松是否会刺激TAG的生物合成，改变肝脏脂肪分解和再酯化过程，并为脂蛋白分泌提供储存的TAG。地塞米松治疗导致TGH表达降低，主要是由于地塞米松诱导的TGH mRNA稳定性降低。地塞米松刺激二酰基甘油酰基转移酶1和2的表达和活性。减少细胞内TAG脂解和增加TAG生物合成的结合导致TAG在地塞米松注射小鼠肝脏内的积累。地塞米松治疗小鼠肝脏TAG分泌率维持在与对照小鼠相似的水平。我们的数据表明，地塞米松刺激新生TAG合成增加了来自新生来源的分泌TAG的比例，同时降低了储存TAG用于分泌的利用率。结果表明，在显著增加的TAG合成过程中，一些TAG从细胞质储存池中转移出来，直接用于内质网腔内的VLDL组装。
Hepatic VLDL (very-low-density lipoprotein) assembly is a complex process that is largely regulated by the provision of lipid for apolipoprotein B assembly. Intracellular stored TAG (triacylglycerol) undergoes an initial lipolysis followed by re-esterification of the lipolytic products to form TAG prior to their incorporation into a VLDL particle. TGH (TAG hydrolase) is a lipase that hydrolyses intracellular TAG within the hepatocyte. We have utilized both dexamethasone-injected mouse and primary hepatocyte models to address whether stimulation of TAG biosynthesis by the synthetic glucocorticoid, dexamethasone, altered hepatic lipolysis and re-esterification and the provision of stored TAG for lipoprotein secretion. Dexamethasone treatment resulted in decreased TGH expression, primarily due to a dexamethasone-induced decrease in TGH mRNA stability. The expression and activities of diacylglycerol acyltransferases 1 and 2 were stimulated by dexamethasone. The combination of reduced intracellular TAG lipolysis and increased TAG biosynthesis contributed to the accumulation of TAG within the livers of dexamethasone-injected mice. The rate of hepatic TAG secretion in dexamethasone-treated mice was maintained at similar levels as in control mice. Our data demonstrate that stimulation of de novo TAG synthesis by dexamethasone increased the proportion of secreted TAG that was derived from de novo sources, while the utilization of stored TAG for secretion was reduced. The results show that, during markedly increased TAG synthesis, some TAGs are diverted from the cytosolic storage pool and are utilized directly for VLDL assembly within the endoplasmic reticulum lumen.