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糖皮质激素对脂肪组织甘油酮生成的影响:系统评价。

Effect of glucocorticoids on glyceroneogenesis in adipose tissue: A systematic review.

机构信息

Laboratory of Physiology, Federal University of São João Del-Rei, Divinópolis, Minas Gerais, Brazil.

Laboratory of Physiology, Federal University of São João Del-Rei, Divinópolis, Minas Gerais, Brazil.

出版信息

Biochimie. 2020 Jan;168:210-219. doi: 10.1016/j.biochi.2019.11.007. Epub 2019 Nov 21.

DOI:10.1016/j.biochi.2019.11.007
PMID:31759936
Abstract

Glyceroneogenesis is important for the maintenance of fat content in white adipose tissue (WAT). An increase in WAT, and especially the pattern of fat distribution, specifically in visceral depots, potentially contributes to cardiovascular and metabolic diseases, such as type 2 diabetes mellitus, myocardial infarction and hypertension. Recent studies have shown important differences in glyceroneogenesis of different fat sites under the administration of glucocorticoids (GCs). Such differences need to be analysed with criteria evidencing the parameter studied, the type of corticoid, the form of administration and also the tissue studied. PubMed, Scopus and Virtual Health Library were used to search for articles that analysed the effect of GCs on glyceroneogenesis in different sites of adipose tissue in mammals and primary cultures. GCs decrease the glyceroneogenesis in epididymal WAT (EWAT) and also decrease the expression of the mRNA, content and activity of phosphoenolpyruvate carboxykinase (PEPCK-C), key enzyme of glyceroneogenesis. However, in retroperitoneal WAT (RWAT), although there is no consensus about the effect of GCs on PEPCK mRNA, GCs increase PEPCK-C activity and glyceroneogenesis flux. In inguinal WAT (IWAT) an in vitro study showed an increase in the PEPCK mRNA induced by dexamethasone. However, prednisolone does not change glyceroneogenesis flux. In interscapular brown adipose tissue (IBAT) prednisolone or dexamethasone does not change PEPCK-C activity in control diet-fed rats but led to a decrease in PEPCK-C activity in fasted- or high-fat/low-carbohydrate diet-fed rats, as well as in suckling rats. Despite that fact that GCs have different potencies, the same dose of dexamethasone reduces PEPCK-C activity in EWAT, but not in RWAT and IBAT from control-diet fed rats. In summary, the data presented in this article show that GCs differentially regulate glyceroneogenesis in different sites of adipose tissue. Further experiments are needed to firmly establish our hypothesis and clarify the mechanisms involved.

摘要

甘油酮生成对于维持白色脂肪组织(WAT)中的脂肪含量很重要。WAT 的增加,特别是脂肪分布的模式,特别是在内脏脂肪库中,可能导致心血管和代谢疾病,如 2 型糖尿病、心肌梗死和高血压。最近的研究表明,糖皮质激素(GCs)给药下不同脂肪部位的甘油酮生成存在重要差异。需要用证据表明研究参数、皮质类固醇类型、给药形式和研究组织的标准来分析这种差异。使用 PubMed、Scopus 和虚拟健康图书馆搜索分析 GC 对哺乳动物和原代培养不同脂肪组织部位甘油酮生成影响的文章。GCs 降低附睾 WAT(EWAT)中的甘油酮生成,也降低甘油酮生成的关键酶磷酸烯醇丙酮酸羧激酶(PEPCK-C)的 mRNA、含量和活性。然而,在腹膜后 WAT(RWAT)中,尽管 GCs 对 PEPCK mRNA 的影响尚无共识,但 GCs 增加了 PEPCK-C 活性和甘油酮生成通量。在腹股沟 WAT(IWAT)中,一项体外研究表明,地塞米松诱导的 PEPCK mRNA 增加。然而,泼尼松龙不会改变甘油酮生成通量。在肩胛间棕色脂肪组织(IBAT)中,泼尼松龙或地塞米松不会改变正常饮食喂养大鼠的 PEPCK-C 活性,但在禁食或高脂肪/低碳水化合物饮食喂养大鼠以及哺乳期大鼠中导致 PEPCK-C 活性降低。尽管 GC 具有不同的效力,但相同剂量的地塞米松可降低 EWAT 中的 PEPCK-C 活性,但不降低正常饮食喂养大鼠的 RWAT 和 IBAT 中的 PEPCK-C 活性。总之,本文提供的数据表明,GCs 可差异化调节不同脂肪组织部位的甘油酮生成。需要进一步的实验来确定我们的假设并阐明所涉及的机制。

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