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Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows.

Imhasly S, Naegeli H, Baumann S, von Bergen M, Luch A, Jungnickel H, Potratz S, Gerspach C - BMC Vet. Res. (2014)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Zürich-Vetsuisse, Institute of Pharmacology and Toxicology, Zürich CH-8057, Switzerland. naegelih@vetpharm.uzh.ch.

ABSTRACT

Background: Hepatic 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.

Results: To 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.

Conclusions: This 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.

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Level of fibrinogen in plasma and total plasma protein concentration in the different groups of dairy cows (mean values of 5–10 animals). (A) Plasma fibrinogen. (B) Total plasma protein. Group 1: no hepatic lipidosis; groups 2–4: progressive stages of hepatic lipidosis. The P values indicate significant differences with the reference group 1; n.s., not significant.
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Figure 2: Level of fibrinogen in plasma and total plasma protein concentration in the different groups of dairy cows (mean values of 5–10 animals). (A) Plasma fibrinogen. (B) Total plasma protein. Group 1: no hepatic lipidosis; groups 2–4: progressive stages of hepatic lipidosis. The P values indicate significant differences with the reference group 1; n.s., not significant.

Mentions: In dairy cows, the excess storage of triacylglycerols in the liver causes progressive hepatocyte damage and, consequently, membrane leakage that results in the increased release of liver enzymes and bile constituents into the blood[2,9]. However, clinical chemical parameters like aspartate aminotransferase (ASAT), γ-glutamyl transferase (GGT), glutamate dehydrogenase (GLDH), sorbitol dehydrogenase (SDH) and bilirubin levels in the blood, being non-specific biomarkers of organ injury, were already elevated in the reference group 1 of cows whose biopsies did not reveal typical features of hepatic lipidosis but that were admitted to the veterinary hospital for other disorders (Table 2). As a general trend, some of these conventional clinical chemistry values (GGT, GLDH and SDH) further increased from group 1 to group 4 (Figure 1), but without being able to discriminate between distinct disease etiologies. Conversely, we observed decreasing plasma fibrinogen concentrations correlating with the gradually enhanced severity of fatty liver disease in groups 2–4 relative to group 1 (Figure 2A), although the overall protein level remained in the normal range (Figure 2B). In summary, these selected clinical chemistry parameters fail to display specificity for the appearance of hepatic lipidosis and, hence, are not sufficient to confirm the diagnosis of this particular disease.


Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows.

Imhasly S, Naegeli H, Baumann S, von Bergen M, Luch A, Jungnickel H, Potratz S, Gerspach C - BMC Vet. Res. (2014)

Level of fibrinogen in plasma and total plasma protein concentration in the different groups of dairy cows (mean values of 5–10 animals). (A) Plasma fibrinogen. (B) Total plasma protein. Group 1: no hepatic lipidosis; groups 2–4: progressive stages of hepatic lipidosis. The P values indicate significant differences with the reference group 1; n.s., not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048253&req=5

Figure 2: Level of fibrinogen in plasma and total plasma protein concentration in the different groups of dairy cows (mean values of 5–10 animals). (A) Plasma fibrinogen. (B) Total plasma protein. Group 1: no hepatic lipidosis; groups 2–4: progressive stages of hepatic lipidosis. The P values indicate significant differences with the reference group 1; n.s., not significant.
Mentions: In dairy cows, the excess storage of triacylglycerols in the liver causes progressive hepatocyte damage and, consequently, membrane leakage that results in the increased release of liver enzymes and bile constituents into the blood[2,9]. However, clinical chemical parameters like aspartate aminotransferase (ASAT), γ-glutamyl transferase (GGT), glutamate dehydrogenase (GLDH), sorbitol dehydrogenase (SDH) and bilirubin levels in the blood, being non-specific biomarkers of organ injury, were already elevated in the reference group 1 of cows whose biopsies did not reveal typical features of hepatic lipidosis but that were admitted to the veterinary hospital for other disorders (Table 2). As a general trend, some of these conventional clinical chemistry values (GGT, GLDH and SDH) further increased from group 1 to group 4 (Figure 1), but without being able to discriminate between distinct disease etiologies. Conversely, we observed decreasing plasma fibrinogen concentrations correlating with the gradually enhanced severity of fatty liver disease in groups 2–4 relative to group 1 (Figure 2A), although the overall protein level remained in the normal range (Figure 2B). In summary, these selected clinical chemistry parameters fail to display specificity for the appearance of hepatic lipidosis and, hence, are not sufficient to confirm the diagnosis of this particular disease.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Zürich-Vetsuisse, Institute of Pharmacology and Toxicology, Zürich CH-8057, Switzerland. naegelih@vetpharm.uzh.ch.

ABSTRACT

Background: Hepatic 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.

Results: To 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.

Conclusions: This 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.

Show MeSH
Related in: MedlinePlus