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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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Serum concentration of diacyl-phosphatidylcholines (mean values of 5–10 animals). (A) Example of metabolite (PC aa C40:3) whose concentration decreased with progressing hepatic lipidosis. Group 1: no hepatic lipidosis; groups 2–4: different stages of hepatic lipidosis. (B) and (C) Diacyl-phosphatidylcholines whose serum concentrations increased with progressing hepatic lipidosis. The P values indicate significant differences with the reference group 1; n.s., not significant.
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Figure 5: Serum concentration of diacyl-phosphatidylcholines (mean values of 5–10 animals). (A) Example of metabolite (PC aa C40:3) whose concentration decreased with progressing hepatic lipidosis. Group 1: no hepatic lipidosis; groups 2–4: different stages of hepatic lipidosis. (B) and (C) Diacyl-phosphatidylcholines whose serum concentrations increased with progressing hepatic lipidosis. The P values indicate significant differences with the reference group 1; n.s., not significant.

Mentions: Two of the 29 discriminating metabolites turned out to be the amino acids glycine (Figure 4A) and glutamine (Figure 4B) with diminished blood levels in the diseased animals of groups 2–4 relative to group 1. However, the majority of metabolites able to discriminate between the reference group 1 and the different stages of fatty liver disease were phosphatidylcholines (PC), i.e. the diacyl-phosphatidylcholines PC aa C30:2, PC aa C32:2, PC aa C36:2, PC aa C36:3, PC aa C36:4, PC aa C38:3, PC aa C38:4, PC aa C38:6, PC aa C40:2, PC aa C40:3, PC aa C40:4 and PC aa C42:2, as well as the acyl-alkyl-phosphatidylcholines PC ae C34:1, PC ae C36:2, PC ae C36:3, PC ae C38:2, PC ae C38:3, PC ae C38:4, PC ae C40:2 and PC ae C40:3 (Table 3). Additional discriminating components in the tested sera included the sphingomyelins SM C18:0 (the only saturated lipid), SM C18:1, SM C24:1 and SM C26:1 as well as the hydroxy-sphingomyelines SM(OH) C22:1, SM (OH) C22:2 and SM (OH) C24:1. As exemplified by PC aa C40:3 in Figure 5A, generally these metabolites showed lower levels in cows with fatty liver disease (groups 2–4) than in the reference animals of group 1. Exceptions were the diacyl-phosphatidylcholines PC aa C30:2 and PC aa C32:2, for which higher levels could be measured in cows with hepatic lipidosis compared to the reference animals (Figures 5B and5C). All lyso-phosphatidylcholines and the sum of hexoses did not show any significant difference between the four groups of early lactating cows.


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)

Serum concentration of diacyl-phosphatidylcholines (mean values of 5–10 animals). (A) Example of metabolite (PC aa C40:3) whose concentration decreased with progressing hepatic lipidosis. Group 1: no hepatic lipidosis; groups 2–4: different stages of hepatic lipidosis. (B) and (C) Diacyl-phosphatidylcholines whose serum concentrations increased with progressing 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 5: Serum concentration of diacyl-phosphatidylcholines (mean values of 5–10 animals). (A) Example of metabolite (PC aa C40:3) whose concentration decreased with progressing hepatic lipidosis. Group 1: no hepatic lipidosis; groups 2–4: different stages of hepatic lipidosis. (B) and (C) Diacyl-phosphatidylcholines whose serum concentrations increased with progressing hepatic lipidosis. The P values indicate significant differences with the reference group 1; n.s., not significant.
Mentions: Two of the 29 discriminating metabolites turned out to be the amino acids glycine (Figure 4A) and glutamine (Figure 4B) with diminished blood levels in the diseased animals of groups 2–4 relative to group 1. However, the majority of metabolites able to discriminate between the reference group 1 and the different stages of fatty liver disease were phosphatidylcholines (PC), i.e. the diacyl-phosphatidylcholines PC aa C30:2, PC aa C32:2, PC aa C36:2, PC aa C36:3, PC aa C36:4, PC aa C38:3, PC aa C38:4, PC aa C38:6, PC aa C40:2, PC aa C40:3, PC aa C40:4 and PC aa C42:2, as well as the acyl-alkyl-phosphatidylcholines PC ae C34:1, PC ae C36:2, PC ae C36:3, PC ae C38:2, PC ae C38:3, PC ae C38:4, PC ae C40:2 and PC ae C40:3 (Table 3). Additional discriminating components in the tested sera included the sphingomyelins SM C18:0 (the only saturated lipid), SM C18:1, SM C24:1 and SM C26:1 as well as the hydroxy-sphingomyelines SM(OH) C22:1, SM (OH) C22:2 and SM (OH) C24:1. As exemplified by PC aa C40:3 in Figure 5A, generally these metabolites showed lower levels in cows with fatty liver disease (groups 2–4) than in the reference animals of group 1. Exceptions were the diacyl-phosphatidylcholines PC aa C30:2 and PC aa C32:2, for which higher levels could be measured in cows with hepatic lipidosis compared to the reference animals (Figures 5B and5C). All lyso-phosphatidylcholines and the sum of hexoses did not show any significant difference between the four groups of early lactating cows.

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