Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos 2600-anexo, 90035-003 Porto Alegre, Rio Grande do Sul, Brazil.
Obes Surg. 2010 May;20(5):633-9. doi: 10.1007/s11695-009-0052-z. Epub 2009 Dec 22.
Visceral adipose tissue is known to release greater amounts of adipokines and free fatty acids into the portal vein, being one of the most predictive factors of nonalcoholic fatty liver disease (NAFLD). Our study has the purpose to evaluate sirtuin 1 (SIRT1), adiponectin, Forkhead/winged helix (FOXO1), peroxisome proliferator-activated receptor (PPAR)gamma1-3, and PPARbeta/delta mRNA expression in morbidly obese patients in three different lipid depots: visceral (VAT), subcutaneous (SAT), and retroperitoneal (RAT). Recent studies suggest that SIRT1, a NAD(+)-dependent deacetylase, protects rats from NAFLD.
We divided the patients in two groups: those with slight or moderate steatosis (hepatic steatosis, HS) and other comprising individuals with severe steatosis associated or not with necroinflammation and fibrosis (severe hepatic steatosis, SHS). The adipose tissue depots were obtained during bariatric surgery. Total RNAs were extracted using TRIzol. The amount of genes of interest was determined by quantitative real-time polymerase chain reaction.
When comparing the two groups of patients, a decrease in SIRT1 was observed in VAT of morbidly obese patients in SHS group (p = 0.006). The mRNA expression of the other genes showed no differences in VAT. No difference was found either in SAT or in RAT for all genes in the study. In addition, the homeostasis model assessment for insulin resistance (HOMA-IR) value was higher in SHS group compared to HS (p = 0.006). Also, our results show that the mRNA expression of SIRT1 and the value of HOMA-IR were positively correlated in VAT of SHS patients (r = 0.654; p = 0.048).
Downregulation of SIRT1 mRNA expression in VAT of SHS could be possible impairing mitochondria biogenesis and fatty acid oxidation, promoting severe steatosis in obese patients. Our results provide a possible proof of SIRT1 protective potential in VAT against NAFLD in humans.
已知内脏脂肪组织向门静脉释放更多的脂肪因子和游离脂肪酸，是预测非酒精性脂肪性肝病（NAFLD）的最具预测性因素之一。我们的研究旨在评估肥胖患者三种不同脂肪组织（内脏脂肪组织（VAT）、皮下脂肪组织（SAT）和腹膜后脂肪组织（RAT）中）中 SIRT1、脂联素、叉头/翼状螺旋转录因子（FOXO1）、过氧化物酶体增殖物激活受体（PPAR）γ1-3 和 PPARβ/δ mRNA 的表达。最近的研究表明，SIRT1 是一种 NAD(+)-依赖性去乙酰化酶，可保护大鼠免受 NAFLD 的影响。
我们将患者分为两组：轻度或中度脂肪变性（肝脂肪变性，HS）和另一组包括伴有或不伴有坏死性炎症和纤维化的严重脂肪变性患者（严重肝脂肪变性，SHS）。在减肥手术期间获取脂肪组织。使用 TRIzol 提取总 RNA。通过定量实时聚合酶链反应确定感兴趣基因的数量。
在比较两组患者时，我们发现 SHS 组肥胖患者 VAT 中的 SIRT1 减少（p = 0.006）。其他基因在 VAT 中的 mRNA 表达没有差异。在研究中的所有基因中，SAT 或 RAT 也没有差异。此外，与 HS 相比，SHS 组的稳态模型评估胰岛素抵抗（HOMA-IR）值更高（p = 0.006）。此外，我们的结果表明，SHS 患者 VAT 中的 SIRT1 mRNA 表达与 HOMA-IR 值呈正相关（r = 0.654；p = 0.048）。
SHS 患者 VAT 中 SIRT1 mRNA 表达下调可能会损害线粒体生物发生和脂肪酸氧化，从而促进肥胖患者的严重脂肪变性。我们的结果提供了 SIRT1 在 VAT 中对 NAFLD 具有保护作用的可能性。
