Limits...
Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows.

Huber K, Dänicke S, Rehage J, Sauerwein H, Otto W, Rolle-Kampczyk U, von Bergen M - Sci Rep (2016)

Bottom Line: In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans.These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria.The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life.

View Article: PubMed Central - PubMed

Affiliation: Institute of Animal Science, University of Hohenheim, Germany.

ABSTRACT
The failure to adapt metabolism to the homeorhetic demands of lactation is considered as a main factor in reducing the productive life span of dairy cows. The so far defined markers of production performance and metabolic health in dairy cows do not predict the length of productive life span satisfyingly. This study aimed to identify novel pathways and biomarkers related to productive life in dairy cows by means of (targeted) metabolomics. In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans. These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria. The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life.

No MeSH data available.


Liver enzymes in healthy (H) and left productive life early (LE) cows.Serum aspartate transaminase (AST) (a) and gamma glutamyl transferase (GGT) (b) activity in cows that left productive life early (LE, black bars, n = 8) or were healthy (H, grey bars, n = 11) as influenced by parturition and onset of lactation. Given were means ± SEM; **p < 0.01. Results of Two-Way ANOVA and Sidak’s multi comparison posttest (Graphpad.prism version 6.0) demonstrate effects of time and grouping and point out interactions between them (results see Table 3 below).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835701&req=5

f4: Liver enzymes in healthy (H) and left productive life early (LE) cows.Serum aspartate transaminase (AST) (a) and gamma glutamyl transferase (GGT) (b) activity in cows that left productive life early (LE, black bars, n = 8) or were healthy (H, grey bars, n = 11) as influenced by parturition and onset of lactation. Given were means ± SEM; **p < 0.01. Results of Two-Way ANOVA and Sidak’s multi comparison posttest (Graphpad.prism version 6.0) demonstrate effects of time and grouping and point out interactions between them (results see Table 3 below).

Mentions: Accordingly, major changes were found in serum concentrations of valerylcarnitine (Fig. 3c), hexadecanoylcarnitine (Fig. 3d), octadecanoylcarnitine (Fig. 3e), hexadecadienylcarnitine (Fig. 3f) and octadecadienylcarnitine (Fig. 3g). The concentrations of these acylcarnitines were higher in H cows compared to LE cows throughout the periparturient period and at any specific time points. The acylcarnitines with double bounds in the fatty acids were already lower ante partum in LE cows indicating hexadecadienylcarnitine and octadecadienylcarnitine as predictive markers relevant for the risk of developing metabolic dysregulation and for leaving productive life early. The biological impact of these differences cannot be defined yet and has to be assessed by further studies. However, these findings led to the hypothesis that higher levels of acylcarnitines in serum of H cows may reflect their capacity to adapt mitochondrial functions properly to the metabolic situation postpartum. Probably hepatic mitochondria are primarily affected, because the liver is discussed to be the main source of serum acylcarnitines16. This could also be suggested for the dairy cow, especially during the transition from pregnancy to lactation when most of ATP is produced by fatty acid oxidation in the liver. However, it was unlikely that the greater concentrations of carnitine and acylcarnitine in serum from H cows were associated with enhanced liver cell death and organ dysfunction. While aspartate transaminase was similar in H and LE cows (Fig. 4a), gamma glutamyl transferase, as a well-known marker for hepatocyte integrity of dairy cows17, was significantly lower in H cows compared to LE cows indicating a less affected liver function in H cows (Fig. 4b). Thus, higher levels of acylcarnitines in serum of H cows appeared to be beneficial. It is suggested that this reflects a greater ability of hepatocytes to release any surplus of carnitine and acylcarnitines from the mitochondria to avoid mitochondria damage. Specific transporters existed in membranes of cells and mitochondria for the uptake or release of carnitine (SLC22A5, OCTN2; novel organic cation transporter 2) and of acylcarnitines (SLC16A9; MCT9, monocarboxylate transporter 9)16. The OCTN2 is known to be upregulated in livers of early lactating cows18 and to be stimulated by PPARα and proinflammatory cytokines in bovine kidney cells19. Since hepatocytes are highly capable of synthesizing carnitine, especially in early lactation1618, an uptake of carnitine appeared to be biologically unnecessary. This indicates an important role of OCTN2 for carnitine export from liver for the use in other peripheral tissues. Information about the existence and regulation of MCT9 transporters in bovine liver is not available so far.


Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows.

Huber K, Dänicke S, Rehage J, Sauerwein H, Otto W, Rolle-Kampczyk U, von Bergen M - Sci Rep (2016)

Liver enzymes in healthy (H) and left productive life early (LE) cows.Serum aspartate transaminase (AST) (a) and gamma glutamyl transferase (GGT) (b) activity in cows that left productive life early (LE, black bars, n = 8) or were healthy (H, grey bars, n = 11) as influenced by parturition and onset of lactation. Given were means ± SEM; **p < 0.01. Results of Two-Way ANOVA and Sidak’s multi comparison posttest (Graphpad.prism version 6.0) demonstrate effects of time and grouping and point out interactions between them (results see Table 3 below).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835701&req=5

f4: Liver enzymes in healthy (H) and left productive life early (LE) cows.Serum aspartate transaminase (AST) (a) and gamma glutamyl transferase (GGT) (b) activity in cows that left productive life early (LE, black bars, n = 8) or were healthy (H, grey bars, n = 11) as influenced by parturition and onset of lactation. Given were means ± SEM; **p < 0.01. Results of Two-Way ANOVA and Sidak’s multi comparison posttest (Graphpad.prism version 6.0) demonstrate effects of time and grouping and point out interactions between them (results see Table 3 below).
Mentions: Accordingly, major changes were found in serum concentrations of valerylcarnitine (Fig. 3c), hexadecanoylcarnitine (Fig. 3d), octadecanoylcarnitine (Fig. 3e), hexadecadienylcarnitine (Fig. 3f) and octadecadienylcarnitine (Fig. 3g). The concentrations of these acylcarnitines were higher in H cows compared to LE cows throughout the periparturient period and at any specific time points. The acylcarnitines with double bounds in the fatty acids were already lower ante partum in LE cows indicating hexadecadienylcarnitine and octadecadienylcarnitine as predictive markers relevant for the risk of developing metabolic dysregulation and for leaving productive life early. The biological impact of these differences cannot be defined yet and has to be assessed by further studies. However, these findings led to the hypothesis that higher levels of acylcarnitines in serum of H cows may reflect their capacity to adapt mitochondrial functions properly to the metabolic situation postpartum. Probably hepatic mitochondria are primarily affected, because the liver is discussed to be the main source of serum acylcarnitines16. This could also be suggested for the dairy cow, especially during the transition from pregnancy to lactation when most of ATP is produced by fatty acid oxidation in the liver. However, it was unlikely that the greater concentrations of carnitine and acylcarnitine in serum from H cows were associated with enhanced liver cell death and organ dysfunction. While aspartate transaminase was similar in H and LE cows (Fig. 4a), gamma glutamyl transferase, as a well-known marker for hepatocyte integrity of dairy cows17, was significantly lower in H cows compared to LE cows indicating a less affected liver function in H cows (Fig. 4b). Thus, higher levels of acylcarnitines in serum of H cows appeared to be beneficial. It is suggested that this reflects a greater ability of hepatocytes to release any surplus of carnitine and acylcarnitines from the mitochondria to avoid mitochondria damage. Specific transporters existed in membranes of cells and mitochondria for the uptake or release of carnitine (SLC22A5, OCTN2; novel organic cation transporter 2) and of acylcarnitines (SLC16A9; MCT9, monocarboxylate transporter 9)16. The OCTN2 is known to be upregulated in livers of early lactating cows18 and to be stimulated by PPARα and proinflammatory cytokines in bovine kidney cells19. Since hepatocytes are highly capable of synthesizing carnitine, especially in early lactation1618, an uptake of carnitine appeared to be biologically unnecessary. This indicates an important role of OCTN2 for carnitine export from liver for the use in other peripheral tissues. Information about the existence and regulation of MCT9 transporters in bovine liver is not available so far.

Bottom Line: In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans.These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria.The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life.

View Article: PubMed Central - PubMed

Affiliation: Institute of Animal Science, University of Hohenheim, Germany.

ABSTRACT
The failure to adapt metabolism to the homeorhetic demands of lactation is considered as a main factor in reducing the productive life span of dairy cows. The so far defined markers of production performance and metabolic health in dairy cows do not predict the length of productive life span satisfyingly. This study aimed to identify novel pathways and biomarkers related to productive life in dairy cows by means of (targeted) metabolomics. In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans. These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria. The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life.

No MeSH data available.