Chronic angiotensin receptor activation promotes hepatic triacylglycerol accumulation during an acute glucose challenge in obese-insulin-resistant OLETF rats.
Chronic angiotensin receptor activation promotes hepatic triacylglycerol accumulation during an acute glucose challenge in obese-insulin-resistant OLETF rats.
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DOI：
10.1007/s12020-021-02834-7
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发表时间：
2022-01
期刊：
影响因子：
3.7
通讯作者：
Ortiz RM
中科院分区：
文献类型：
--
作者：
Godoy-Lugo JA;Thorwald MA;Hui DY;Nishiyama A;Nakano D;Soñanez-Organis JG;Ortiz RM
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AT1过度激活与MetS期间非酒精性脂肪性肝病（NAFLD）之间的联系。采用四组25周龄大鼠：(1)不给药LETO，(2)不给药OLETF， (3) OLETF +血管紧张素受体阻滞剂（ARB； 10mg奥美沙坦/kg/d × 8周）和(4)OLETF±ARB （MINUS； 10mg奥美沙坦/kg/d × 4周，然后去除直至剥离）。为了研究代谢的动态变化，动物在口服葡萄糖刺激后（空腹，葡萄糖后3和6小时）被解剖。与OLETF相比，ARB患者血浆总胆固醇和TAG保持不变。然而，ARB组的肝TAG比OLETF组低55%，并且在整个挑战过程中保持较低水平。ARB患者的基础CD36和ApoB分别比OLETF患者低28%和29%。ARB中PRDX6丰度比OLETF低45%，且与ARB中肝脏TAG呈负相关。慢性阻断AT1可保护肝脏免受葡萄糖过载时TAG的积累。这可以通过调节NEFA摄取和通过ApoB增加TAG输出来实现。我们的研究强调了AT1信号对肝脏底物代谢受损的贡献，以及高糖负荷的危害及其对MetS期间脂肪变性的潜在贡献。
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. 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). 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. 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.
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影响因子：
2.9
作者：
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通讯作者：
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影响因子：
2.1
作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0404297101
发表时间：
2004-08-03
影响因子：
11.1
作者：
Chen, GX;Liang, GS;Brown, MS
通讯作者：
Brown, MS