Glucose Increases Hepatic Mitochondrial Antioxidant Enzyme Activities in Insulin Resistant Rats Following Chronic Angiotensin Receptor Blockade.
Glucose Increases Hepatic Mitochondrial Antioxidant Enzyme Activities in Insulin Resistant Rats Following Chronic Angiotensin Receptor Blockade.
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DOI：
10.3390/ijms231810897
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发表时间：
2022-09-17
影响因子：
5.6
通讯作者：
Ortiz, Rudy M.
中科院分区：
文献类型：
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作者：
Godoy-Lugo, Jose A.;Thorwald, Max A.;Mendez, Dora A.;Rodriguez, Ruben;Nakano, Daisuke;Nishiyama, Akira;Ortiz, Rudy M.
非酒精性脂肪性肝病（NAFLD）影响着世界上20%的人口。1型血管紧张素受体（AT 1）的过度激活导致代谢功能障碍和氧化剂产生增加，这与NAFLD和肝脏脂质代谢受损有关。核因子红细胞-2相关因子2（Nrf 2）通过与抗氧化反应元件（ARE）结合来调节抗氧化剂II期基因的表达;然而，在NAFLD的进展过程中，AT 1促进这一途径的机制尚未得到解决。为了研究肝脏Nrf 2对高血糖激发的反应，我们研究了三组大鼠（雄性，10周龄）：（1）未给药的瘦型Long Evans德岛大冢（LETO），（2）未给药的肥胖型大冢Long Evans德岛脂肪（OLETF），和（3）OLETF +血管紧张素受体阻滞剂（OLETF + ARB; 10 mg奥美沙坦/kg/d × 6周）。在禁食过夜（T0;基线）以及口服葡萄糖负荷后1 h和2 h采集肝脏。在基线时，慢性AT 1阻断增加了核Nrf 2含量，降低了谷氨酸-半胱氨酸连接酶催化（GCLC）亚基、谷胱甘肽过氧化物酶1（GPx 1）和超氧化物歧化酶2（SOD 2）的表达，线粒体过氧化氢酶活性和肝脏4-羟基-2-壬烯醛（4-HNE）含量。AT 1阻断后，与肝纤维化相关的肝脏白细胞介素-1 β（IL-1β）和IV型胶原蛋白的表达减少。葡萄糖增加了OLETF中的Nrf 2易位，但在ARB中减少，这表明葡萄糖诱导了抗氧化防御的需要，而ARB可以改善这种需要。这些结果表明，AT 1的过度激活通过抑制Nrf 2促进氧化损伤，并促进与NAFLD发展相关的肝纤维化。
Non-alcoholic fatty liver disease (NAFLD) affects up to 20% of the world’s population. Overactivation of the angiotensin receptor type 1 (AT1) contributes to metabolic dysfunction and increased oxidant production, which are associated with NAFLD and impaired hepatic lipid metabolism. Nuclear factor erythroid-2-related factor 2 (Nrf2) regulates the expression of antioxidant phase II genes by binding to the antioxidant response element (ARE); however, the mechanisms by which AT1 contributes to this pathway during the progression of NAFLD remain unresolved. To investigate hepatic Nrf2 response to a hyperglycemic challenge, we studied three groups of rats (male, 10-weeks-old): (1) untreated, lean Long Evans Tokushima Otsuka (LETO), (2) untreated, obese Otsuka Long Evans Tokushima Fatty (OLETF), and (3) OLETF + angiotensin receptor blocker (OLETF + ARB; 10 mg olmesartan/kg/d × 6 weeks). Livers were collected after overnight fasting (T0; baseline), and 1 h and 2 h post-oral glucose load. At baseline, chronic AT1 blockade increased nuclear Nrf2 content, reduced expression of glutamate-cysteine ligase catalytic (GCLC) subunit, glutathione peroxidase 1 (GPx1), and superoxide dismutase 2 (SOD2), mitochondrial catalase activity, and hepatic 4-hydroxy-2-nonenal (4-HNE) content. The expression of hepatic interleukin-1 beta (IL-1β) and collagen type IV, which are associated with liver fibrosis, were decreased with AT1 blockade. Glucose increased Nrf2 translocation in OLETF but was reduced in ARB, suggesting that glucose induces the need for antioxidant defense that is ameliorated with ARB. These results suggest that overactivation of AT1 promotes oxidant damage by suppressing Nrf2 and contributing to hepatic fibrosis associated with NAFLD development.
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影响因子：
3.7
作者：
Godoy-Lugo JA;Thorwald MA;Hui DY;Nishiyama A;Nakano D;Soñanez-Organis JG;Ortiz RM
通讯作者：
Ortiz RM
影响因子：
82.9
作者：
Friedman SL;Neuschwander-Tetri BA;Rinella M;Sanyal AJ
通讯作者：
Sanyal AJ
影响因子：
5.1
作者：
Cui, R.;Gao, M.;Qu, S.;Liu, D.
通讯作者：
Liu, D.
影响因子：
2.1
作者：
Ghasemi A;Zahediasl S
通讯作者：
Zahediasl S
DOI：
10.3390/antiox11050927
发表时间：
2022-05-09
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
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作者：
通讯作者：
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