Abstract
Simple SummarySirtuin 1 (SIRT1), a NAD-dependent histone deacetylase, is involved in oxidative stress and lipid metabolism regulation. Limited studies exist regarding the role of SIRT1 in lipid metabolism disorder in periparturient dairy cows. This study explores the effect of hepatic steatosis on the expression of the SIRT1 gene and protein and the proteins encoded by the genes downstream to it, all of which are involved in lipid metabolism in the liver. Control cows (n = 6, parity 3.0 ± 2.0, milk production 28 ± 47 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). The present study indicates that low SIRT1 expression caused by hepatic steatosis promotes hepatic fatty acid synthesis and inhibits fatty acid β-oxidation. We believe that our study makes a significant contribution to the literature because it demonstrates that hepatic steatosis is associated with increased hepatic fatty acid synthesis, inhibited fatty acid β-oxidation and reduced lipid transport.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) (p < 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) (p < 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 (p < 0.05). Lower enzyme activities of SIRT1, PGC-1α, Cu/Zn SOD, CAT, GSH-Px, SREBP-1c and Mn SOD (p < 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.
Highlights
Dairy cows undergo negative energy balance (NEB) when they transition from late gestation to early lactation, during which ketosis, fatty liver and metritis are likely to occur [1,2]
We report that the knocked down expression or overexpression of sirtuin 1 (SIRT1) results in changes in the lipid/cholesterol (Chol) levels in the serum and liver, and causes accumulation of lipids in the liver, a process leading to hepatic steatosis [20,21]
Our study showed that fatty liver significantly milk yield, the milk protein and milk urea nitrogen (MUN), and significantly increased Somatic cell counts (SCC), which indicates that fatty liver decreased dry matter intake (DMI), milk yield, the milk protein and MUN, and significantly increased SCC, which decreased the milk production and negatively affect milk quality
Summary
Dairy cows undergo negative energy balance (NEB) when they transition from late gestation to early lactation, during which ketosis, fatty liver and metritis are likely to occur [1,2]. The occurrence of fatty liver in dairy cows increases treatment costs and culling and decreased milk production [3]. Fatty liver disease develops when increased infectious and metabolic diseases are likely to occur [4,5]. For these reasons, fatty liver has become a major international health burden in dairy cows. SIRT1 is highly sensitive to intracellular redox status and provides cells with the ability to tolerate oxidative stress. SIRT1 protects cells from oxidative stress by increasing the activity of catalase [7,8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
