PURPOSE Angiotensin receptor blockers (ARBs) can ameliorate metabolic syndrome (MetS)-associated dyslipidemia, hepatic steatosis, and glucose intolerance, suggesting that angiotensin receptor (AT1) over-activation contributes to impaired lipid and glucose metabolism, which is characteristic of MetS. The aim of this study was to evaluate changes in the lipid profile and proteins of fatty acid uptake, triacylglycerol (TAG) synthesis, and β-oxidation to better understand the links between AT1 overactivation and non-alcoholic fatty liver disease (NAFLD) during MetS. METHODS Four groups of 25-week-old-rats were used: (1) untreated LETO, (2) untreated OLETF, (3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d × 8 weeks) and (4) OLETF ± ARB (MINUS; 10 mg olmesartan/kg/d × 4 weeks, then removed until dissection). To investigate the dynamic shifts in metabolism, animals were dissected after an oral glucose challenge (fasting, 3 and 6 h post-glucose). RESULTS Compared to OLETF, plasma total cholesterol and TAG remained unchanged in ARB. However, liver TAG was 55% lesser in ARB than OLETF, and remained lower throughout the challenge. Basal CD36 and ApoB were 28% and 29% lesser, respectively, in ARB than OLETF. PRDX6 abundance in ARB was 45% lesser than OLETF, and it negatively correlated with liver TAG in ARB. CONCLUSIONS Chronic blockade of AT1 protects the liver from TAG accumulation during glucose overload. This may be achieved by modulating NEFA uptake and increasing TAG export via ApoB. Our study highlights the contributions of AT1 signaling to impaired hepatic substrate metabolism and the detriments of a high-glucose load and its potential contribution to steatosis during MetS.

中文翻译：

---

在肥胖胰岛素抵抗的 OLETF 大鼠急性葡萄糖挑战期间，慢性血管紧张素受体激活促进肝脏三酰基甘油积累。

目的血管紧张素受体阻滞剂 (ARBs) 可以改善代谢综合征 (MetS) 相关的血脂异常、肝脂肪变性和葡萄糖耐受不良，这表明血管紧张素受体 (AT1) 过度激活会导致脂质和葡萄糖代谢受损，这是 MetS 的特征。本研究的目的是评估脂肪酸摄取、三酰基甘油 (TAG) 合成和 β-氧化的脂质谱和蛋白质的变化，以更好地了解在 MetS 期间 AT1 过度激活与非酒精性脂肪肝病 (NAFLD) 之间的联系. 方法 使用四组 25 周龄大鼠：(1) 未处理的 LETO，(2) 未处理的 OLETF，(3) OLETF + 血管紧张素受体阻滞剂 (ARB；10 mg 奥美沙坦/kg/d × 8 周) 和 ( 4) OLETF ± ARB (MINUS; 10 mg olmesartan/kg/d × 4 周，然后取出直至解剖)。为了研究代谢的动态变化，在口服葡萄糖激发后（禁食，葡萄糖后 3 和 6 小时）解剖动物。结果 与 OLETF 相比，ARB 中的血浆总胆固醇和 TAG 保持不变。然而，ARB 中的肝脏 TAG 比 OLETF 低 55%，并且在整个挑战过程中保持较低。ARB 中的基础 CD36 和 ApoB 分别比 OLETF 低 28% 和 29%。ARB 中的 PRDX6 丰度比 OLETF 低 45%，并且与 ARB 中的肝脏 TAG 呈负相关。结论 AT1 的慢性阻断可保护肝脏在葡萄糖超负荷期间免受 TAG 积累。这可以通过调节 NEFA 摄取和通过 ApoB 增加 TAG 输出来实现。