Li Yu, Zou Suping, Ding Hongyan, Hao Ning, Huang Yingying, Tang Jishun, Cheng Jianbo, Feng Shibin, Li Jinchun, Wang Xichun, Wu Jinjie
College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.
Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Hefei 230036, China.
Animals (Basel). 2020 Mar 27;10(4):560. doi: 10.3390/ani10040560.
Dairy cows usually experience negative energy balance coupled with an increased incidence of fatty liver during the periparturient period. The purpose of this study was to investigate the effect of hepatic steatosis on the expression of the sirtuin 1 (SIRT1), along with the target mRNA and protein expressions and activities related to lipid metabolism in liver tissue. Control cows (n = 6, parity 3.0 ± 2.0, milk production 28 ± 7 kg/d) and mild fatty liver cows (n = 6, parity 2.3 ± 1.5, milk production 20 ± 6 kg/d) were retrospectively selected based on liver triglycerides (TG) content (% wet liver). Compared with the control group, fatty liver cows had greater concentrations of cholesterol and TG along with the typically vacuolated appearance and greater lipid droplets in the liver. Furthermore, fatty liver cows had greater mRNA and protein abundance related to hepatic lipid synthesis proteins sterol regulatory element binding proteins (SREBP-1c), long-chain acyl-CoA synthetase (ACSL), acyl-CoA carbrolase (ACC) and fatty acid synthase (FAS) and lipid transport proteins Liver fatty acid binding protein (L-FABP), apolipoprotein E (ApoE), low density lipoprotein receptor (LDLR) and microsomal TG transfer protein (MTTP) ( < 0.05). However, they had lower mRNA and protein abundance associated with fatty acid β-oxidation proteins SIRT1, peroxisome proliferator-activated receptor co-activator-1 (PGC-1α), peroxisome proliferator-activated receptor-α (PPARα), retinoid X receptor (RXRα), acyl-CoA 1 (ACO), carnitine palmitoyltransferase 1 (CPT1), carnitine palmitoyltransferase 2 (CPT2) and long- and medium-chain 3-hydroxyacyl-CoA dehydrogenases (LCAD) ( < 0.05). Additionally, mRNA abundance and enzyme activity of enzymes copper/zinc superoxide dismutase (Cu/Zn SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and manganese superoxide dismutase (Mn SOD) decreased and mRNA and protein abundance of p45 nuclear factor-erythroid 2 (p45 NF-E2)-related factor 1 (Nrf1), mitochondrial transcription factor A (TFAM) decreased ( < 0.05). Lower enzyme activities of SIRT1, PGC-1α, Cu/Zn SOD, CAT, GSH-Px, SREBP-1c and Mn SOD ( < 0.05) and concentration of reactive oxygen species (ROS) were observed in dairy cows with fatty liver. These results demonstrate that decreased SIRT1 associated with hepatic steatosis promotes hepatic fatty acid synthesis and inhibits fatty acid β-oxidation. Hence, SIRT1 may represent a novel therapeutic target for the treatment of the fatty liver disease in dairy cows.
奶牛在围产期通常会经历负能量平衡，同时脂肪肝的发病率增加。本研究的目的是调查肝脂肪变性对沉默调节蛋白1（SIRT1）表达的影响，以及与肝组织脂质代谢相关的靶mRNA和蛋白表达及活性。根据肝脏甘油三酯（TG）含量（肝脏湿重百分比）回顾性选择对照奶牛（n = 6，胎次3.0 ± 2.0，产奶量28 ± 7 kg/d）和轻度脂肪肝奶牛（n = 6，胎次2.3 ± 1.5，产奶量20 ± 6 kg/d）。与对照组相比，脂肪肝奶牛的胆固醇和TG浓度更高，肝脏呈现典型的空泡化外观且脂滴更多。此外，脂肪肝奶牛与肝脏脂质合成蛋白固醇调节元件结合蛋白（SREBP-1c）、长链脂酰辅酶A合成酶（ACSL）、酰基辅酶A羧化酶（ACC）和脂肪酸合酶（FAS）以及脂质转运蛋白肝脏脂肪酸结合蛋白（L-FABP）、载脂蛋白E（ApoE）、低密度脂蛋白受体（LDLR）和微粒体TG转运蛋白（MTTP）相关的mRNA和蛋白丰度更高（P < 0.05）。然而，它们与脂肪酸β氧化蛋白SIRT1、过氧化物酶体增殖物激活受体共激活因子-1（PGC-1α）、过氧化物酶体增殖物激活受体-α（PPARα）、视黄酸X受体（RXRα）、酰基辅酶A 1（ACO）、肉碱棕榈酰转移酶1（CPT1）、肉碱棕榈酰转移酶2（CPT2）以及长链和中链3-羟基酰基辅酶A脱氢酶（LCAD）相关的mRNA和蛋白丰度更低（P < 0.05）。此外，铜/锌超氧化物歧化酶（Cu/Zn SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）和锰超氧化物歧化酶（Mn SOD）的mRNA丰度和酶活性降低，p45核因子-红细胞2（p45 NF-E2）相关因子1（Nrf1）、线粒体转录因子A（TFAM）的mRNA和蛋白丰度降低（P < 0.05）。在患有脂肪肝的奶牛中观察到SIRT1、PGC-1α、Cu/Zn SOD、CAT、GSH-Px、SREBP-1c和Mn SOD的酶活性较低（P < 0.05）以及活性氧（ROS）浓度较低。这些结果表明，与肝脂肪变性相关的SIRT1减少促进肝脏脂肪酸合成并抑制脂肪酸β氧化。因此，SIRT1可能是治疗奶牛脂肪肝疾病的一个新的治疗靶点。
