Adaptations of hepatic lipid metabolism and mitochondria in dairy cows with mild fatty liver

Abstract

The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. Fatty liver is one of the main health disorders after parturition. Therefore, to investigate changes in hepatic lipid metabolic status and mitochondria in dairy cows with mild fatty liver, liver and blood samples were collected from healthy cows (n = 15) and cows with mild fatty liver (n = 15). To determine the effects of palmitic acids (PA), one of the major component of fatty acids, on lipid metabolism and mitochondria in vitro, calf hepatocytes were isolated from healthy calves and treated with various concentrations of PA (0, 50, 100, and 200 μM). Dairy cows with mild fatty liver displayed hepatic lipid accumulation. The protein levels of sterol regulatory element-binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptor-α (PPARα) and mRNA levels of acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), acyl-CoA oxidase (ACO), and carnitine palmitoyltransferase 1A (CPT1A) were significantly higher in dairy cows with mild fatty liver than in control cows. The hepatic mitochondrial DNA content, mRNA levels of oxidative phosphorylation complexes I to V (CO 1-V), protein levels of cytochrome c oxidase subunit IV (COX IV), voltage dependent anion channel 1 (VDAC1), peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), and adenosine triphosphate (ATP) content were all markedly increased in the liver of dairy cows with mild fatty liver compared with healthy cows. The PA treatment significantly increased lipid accumulation; protein levels of SREBP-1c and PPARα; and mRNA levels of ACC1, FAS, ACO, and CPT1A in calf hepatocytes. Moreover, the mitochondrial DNA content, mRNA levels of CO 1-V, protein levels of COX IV, VDAC1, PGC-1α, NRF1, mitochondrial transcription factor A, and ATP content were significantly increased in PA-treated hepatocytes compared with control hepatocytes. The protein level of mitofusin-2 was significantly decreased in PA-treated groups. In conclusion, lipid synthesis and oxidation, number of mitochondria, and ATP production were increased in the liver of dairy cows with mild fatty liver and PA-treated calf hepatocytes. These changes in hepatic mitochondria and lipid metabolism may be the adaptive mechanism of dairy cows with mild fatty liver.

Perilipin 5 promotes hepatic steatosis in dairy cows through increasing lipid synthesis and decreasing very low density lipoprotein assembly

“…Those responses were further accompanied by increased lipid synthesis and inhibition of VLDL assembly. Hence, data from the present study extend the study of processes related to fatty liver development in dairy cows by Du et al (2018a).…”

“…Thus, cows with moderate fatty liver were selected in this study. Notably, in this study, the hepatic TAG content of dairy cows with fatty liver was 8.03% (g/g of wet weight) compared with 3.01% (g/g of wet weight) in the study of Du et al (2018a). Thus, clearly, the present study resulted in a more pronounced degree of TAG accumulation in the liver.…”

“…Excessive amounts of fatty acids entering the liver are re-esterified and stored as TAG in hepatocytes, which results in fatty liver. Our previous study found that lipid synthesis and number of mitochondria increased in the liver of dairy cows with mild fatty liver, which we speculated were adaptive mechanisms of the liver in response to NEB (Du et al, 2018a). In the present study, we preselected 25 cows with suspected fatty liver and found that 16 cows had fatty liver, 13 of which were moderate fatty liver (hepatic TAG content 5-10%) and 3 of which were mild fatty liver (hepatic TAG content 1-5%).…”

Impaired hepatic autophagic activity in dairy cows with severe fatty liver is associated with inflammation and reduced liver function

“…The ultrastructural characteristics of autophagosomes were visualized by transmission electron microscopy (Lei et al, 2016;Du et al, 2018a). Liver biopsies were fixed with 2.5% glutaraldehyde and 2% paraformaldehyde at 4°C for 12 h and then postfixed in 1% osmium tetroxide for 1 h. Subsequently, liver biopsies were dehydrated in an ethanol series and infiltrated with Spurr's resin.…”

The effect of metabolism on the course of labor and the postpartum period in highly productive cows

“…Industrial technology for producing livestock products involves the constant adaptation of animals to the effects of various adverse stress factors caused by conditions of keeping, feeding, exploitation [6][7][8][9]. The most pronounced negative effect of such factors is exerted on pregnant cows, in the body of which increased energy consumption occurs, caused by intensive exploitation and development of the fetus [10,11], which leads to the intensive use of plastic tissue compounds, primarily deposited fat, and hereinafter, structural lipids [4,12,13].…”