Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows

Abstract

BackgroundHepatic lipidosis or fatty liver disease is a major metabolic disorder of high-producing dairy cows that compromises animal performance and, hence, causes heavy economic losses worldwide. This syndrome, occurring during the critical transition from gestation to early lactation, leads to an impaired health status, decreased milk yield, reduced fertility and shortened lifetime. Because the prevailing clinical chemistry parameters indicate advanced liver damage independently of the underlying disease, currently, hepatic lipidosis can only be ascertained by liver biopsy. We hypothesized that the condition of fatty liver disease may be accompanied by an altered profile of endogenous metabolites in the blood of affected animals.ResultsTo identify potential small-molecule biomarkers as a novel diagnostic alternative, the serum samples of diseased dairy cows were subjected to a targeted metabolomics screen by triple quadrupole mass spectrometry. A subsequent multivariate test involving principal component and linear discriminant analyses yielded 29 metabolites (amino acids, phosphatidylcholines and sphingomyelines) that, in conjunction, were able to distinguish between dairy cows with no hepatic lipidosis and those displaying different stages of the disorder.ConclusionsThis proof-of-concept study indicates that metabolomic profiles, including both amino acids and lipids, distinguish hepatic lipidosis from other peripartal disorders and, hence, provide a promising new tool for the diagnosis of hepatic lipidosis. By generating insights into the molecular pathogenesis of hepatic lipidosis, metabolomics studies may also facilitate the prevention of this syndrome.

Investigation of coagulation and serum biochemistry profiles in dairy cattle with different degrees of fatty liver

“…We could not detect any differences in fibrinogen con centrations between different degrees of fatty liver, which is not in agreement with recent results (Imhasly et al, 2014) where fibrinogen concentration was nega tively correlated with the degree of lipid infiltration in the liver. Hypofibrinogenemia results from hyperfi brinolysis due to chronic liver disease (Irmak et al, 2006), but can also be associated with DIC in cattle with inflammatory disease (Thomson et al, 1974).…”

“…In cows with LDA, alterations in clotting profiles have been observed and were suspected to be caused by impaired liver function (Irmak and Turgut, 2005;Sobiech et al, 2008). A recent study revealed a negative correlation between plasma fibrinogen concen tration and lipid infiltration in the liver which was at tributed to impaired liver function in advanced liver disease due to lipid infiltration (Imhasly et al, 2014).…”

“…After cutting in 2 3µm thin sections, mounting on glass slides and staining with hematoxylin eosin (H&E), the histological lesions were staged into 4 categories, as de scribed elsewhere (Imhasly et al, 2014).…”

Plasma Biomarkers of Poor Muscle Quality in Older Men and Women from the Baltimore Longitudinal Study of Aging

“…However, very little research has focused on the identification of metabolic biomarkers for poor muscle mass and strength in older adults (11). Here we report the findings of a pilot cross-sectional, nested case-control study using a targeted metabolomics approach, where the concentrations of 180 metabolites belonging to six classes (amino acids, biogenic amines, amino acid metabolites, acyl carnitines, glycerolphospholipids, sphingomyelins, and glucose) were determined by LC MS/MS, using the Biocrates p180 system (15,16). In particular, we contrasted plasma metabolites concentrations between 79 participants with low muscle quality ratio versus 79 controls with high muscle quality who were matched by age, sex, and height.…”

“…Metabolomics, unlike the other -omics, provides a direct signature of the metabolic state of the organism (12)(13)(14). Recent advances in mass spectrometry allow the simultaneous analysis of hundreds of metabolites from small amounts of biological material (15,16). It is assumed that the biological pathways leading to pathologic conditions causes altered concentrations of specific metabolites and that studying a subset of these metabolites may offer important clues on the pathophysiology of these conditions.…”