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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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Related in: MedlinePlus

Combined principal component and linear discriminant analysis. This model reveals that 29 endogenous metabolites, in conjunction, distinguish dairy cows with different stages of hepatic lipidosis (groups 2–4) from reference animals (group 1) lacking the characteristic lipid deposition in their liver. The centroid, or center of mass, were computed from the coordinates of all points in each group. The linear functions for the two main discriminant factors [F (x1) and F (x2)] are laid down in the “Methods” section.
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Figure 3: Combined principal component and linear discriminant analysis. This model reveals that 29 endogenous metabolites, in conjunction, distinguish dairy cows with different stages of hepatic lipidosis (groups 2–4) from reference animals (group 1) lacking the characteristic lipid deposition in their liver. The centroid, or center of mass, were computed from the coordinates of all points in each group. The linear functions for the two main discriminant factors [F (x1) and F (x2)] are laid down in the “Methods” section.

Mentions: To expand the spectrum of biomarkers that accompany hepatic lipidosis in dairy cows, the AbsoluteIDQ system was applied in conjunction with triple quadrupole mass spectrometry to compare the serum metabolites of animals that did not show any lipid storage in liver cells (reference group 1) and the corresponding groups 2–4 displaying various stages of the syndrome. The AbsoluteIDQ metabolomic platform allows for the accurate identification and quantitative measurement of 163 endogenous metabolites from different compound classes, including amino acids, carbohydrates, carnitines, sphingolipids and phosphatidylcholines[29-31]. A multivariate statistical model revealed 29 metabolites, listed in Table 3, who could be used to separate the hepatic lipidosis groups 2 to 4 from the reference group 1. To graphically illustrate the clear separation between groups achieved by this set of metabolic endpoints, the data were subjected to principal component and linear discriminant analyses (Figure 3). Using the loading factors for linear discriminant function 1 outlined in the “Methods” section, we identified 6 phosphatidylcholines that contributed the most to the observed separation and could therefore be regarded as a promising predictive biomarkers of hepatic lipidosis: PC aa C30:2, PC aa C32:2, PC aa C36:3, PC aa C38:3, PC aa C36:4 and PC ae C36:2).


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)

Combined principal component and linear discriminant analysis. This model reveals that 29 endogenous metabolites, in conjunction, distinguish dairy cows with different stages of hepatic lipidosis (groups 2–4) from reference animals (group 1) lacking the characteristic lipid deposition in their liver. The centroid, or center of mass, were computed from the coordinates of all points in each group. The linear functions for the two main discriminant factors [F (x1) and F (x2)] are laid down in the “Methods” section.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Combined principal component and linear discriminant analysis. This model reveals that 29 endogenous metabolites, in conjunction, distinguish dairy cows with different stages of hepatic lipidosis (groups 2–4) from reference animals (group 1) lacking the characteristic lipid deposition in their liver. The centroid, or center of mass, were computed from the coordinates of all points in each group. The linear functions for the two main discriminant factors [F (x1) and F (x2)] are laid down in the “Methods” section.
Mentions: To expand the spectrum of biomarkers that accompany hepatic lipidosis in dairy cows, the AbsoluteIDQ system was applied in conjunction with triple quadrupole mass spectrometry to compare the serum metabolites of animals that did not show any lipid storage in liver cells (reference group 1) and the corresponding groups 2–4 displaying various stages of the syndrome. The AbsoluteIDQ metabolomic platform allows for the accurate identification and quantitative measurement of 163 endogenous metabolites from different compound classes, including amino acids, carbohydrates, carnitines, sphingolipids and phosphatidylcholines[29-31]. A multivariate statistical model revealed 29 metabolites, listed in Table 3, who could be used to separate the hepatic lipidosis groups 2 to 4 from the reference group 1. To graphically illustrate the clear separation between groups achieved by this set of metabolic endpoints, the data were subjected to principal component and linear discriminant analyses (Figure 3). Using the loading factors for linear discriminant function 1 outlined in the “Methods” section, we identified 6 phosphatidylcholines that contributed the most to the observed separation and could therefore be regarded as a promising predictive biomarkers of hepatic lipidosis: PC aa C30:2, PC aa C32:2, PC aa C36:3, PC aa C38:3, PC aa C36:4 and PC ae C36:2).

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