The effect of different treatments for early-lactation hyperketonemia on liver triglycerides, glycogen, and expression of key metabolic enzymes in dairy cattle

Abstract

Despite the widespread use of treatments for postpartum hyperketonemia in dairy cows, there is currently a lack of evidence comparing their effects on both the resolution of hyperketonemia and the potential effects on the liver of affected animals. The objective of our work was to investigate the effect of commonly used hyperketonemia treatments on hepatic triglyceride and glycogen content as well as on the mRNA and protein abundance of key enzymes involved in gluconeogenesis, ketogenesis, and lipid metabolism. Multiparous Holstein cows between 3 and 9 d in milk were screened 3 times per week and enrolled in the study when whole-blood β-hydroxybutyrate concentrations measured ≥1.2 mmol/L. Cows were randomly allocated to 1 of 4 groups: (1) 500 mL of a 50% d-glucose solution intravenously once a day for 3 d (n = 8), (2) 300 mL of propylene glycol orally once a day for 3 d (n = 8), (3) 500 mL of a 50% d-glucose solution intravenously and 300 mL of propylene glycol orally once a day for 3 d (n = 8), or (4) an untreated control group (n = 8). Liver biopsies were taken on the day of enrollment as well as on the day following completion of treatments. Liver triglyceride and glycogen content were determined by colorimetric and fluorometric methods, respectively. Gene and protein expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase 1, glucose-6-phosphatase, 3-hydroxy-3-methylglutaryl-CoA synthase 2, acetyl-CoA carboxylase, and carnitine palmitoyltransferase 1A were compared between groups and time points using quantitative reverse transcriptase PCR and Western blotting techniques, respectively. In addition, the ratio of light chain 3B II:I was determined by Western blotting. Plasma samples from both time points for each enrolled cow were submitted for chemistry analysis. Data were analyzed using a repeated-measures ANOVA taking into account the paired nature of the data, and differences between all groups and time points were controlled for multiple comparisons using the Tukey procedure. No difference was found in triglyceride or glycogen concentration between treatment groups. The gene expression of pyruvate carboxylase decreased in the group receiving both treatments, whereas protein expression of this enzyme increased in all groups over time. The autophagy marker light chain 3B II:I decreased in the group receiving both glucose and propylene glycol. No other changes in gene or protein expression of key hepatic enzymes were associated with treatments. We conclude that intravenous glucose and oral propylene glycol, commonly used treatments for ketosis in postpartum dairy cows, administered alone or in combination for a duration of 3 d did not have important beneficial or detrimental effects on selected indicators of liver composition and function in cows with hyperketonemia.

Effects of a Multicomponent Herbal Extract on the Course of Subclinical Ketosis in Dairy Cows – a Blinded Placebo-controlled Field-study

“…At milking time 28, the interaction of initial ketosis severity and ▶ Fig. 3 Development of various blood plasma parameters of cows with subclinical ketosis treatment with sodium propionate (SP), herbal extract (HE), or placebo (PL) orally administered 10 times (twice daily) from milking time 1 until milking time 10; concentrations of beta-hydroxybutyrate (BHB) (a), glucose (b), nonesterified fatty acids (NEFA) (c), GGT (d), and GLDH (e) are shown before treatment (milking time 0), 4 (milking time 14), and 18 (milking time 28) milking times after the end of the treatment for either KET-low (84 cows with initial cow-side blood-BHB ≥ 1.0 mmol/L and ≤ 1.2 mmol/L) or KET-high (39 cows with initial cow-side blood-BHB > 1.2 mmol/L) cows. Boxplots represent raw data.…”

“…The few studies available focused primarily on propylene glycol as medication, but only McArt et al described propylene glycol alone as subclinical ketotic treatment compared to placebo (PL) [11,12]. Propylene glycol was tested for treatment of subclinical ketosis in various combinations by adding niacin, insulin or butaphosphane-cyanocobalamin, glucocorticoids, glucose, or L-carnitine and methionine [13][14][15][16][17][18][19]. Glucose precursors like propylene glycol or sodium propionate (SP) were orally administered for 3 to 7 days as standard therapy in subclinical ketotic dairy cows in former studies (Fig.…”

“…1S, Supporting Information). In many studies, hyperketotic cows were treated regardless of the presence or absence of clinical signs [13][14][15][16][17]19]. Sahoo et al (2009) administered dextrose, dexamethasone, and antioxidants to subclinically ketotic cows with confirmed ketone bodies in their urine [20].…”

Liver phosphorus content and liver function in states of phosphorus deficiency in transition dairy cows

“…Upregulation of this enzyme as it was predominantly observed in LP cows has been reported to occur in healthy dairy cows after calving [48]. ACC, an enzyme of the fatty acid biosynthesis catalyzing the conversion from acetyl CoA to malonyl-CoA was the only enzyme for which a weak but significant treatment effect was identified [49]. Slightly higher values in LP than in C cows are indicative of higher hepatic de-novo lipid synthesis in states of P-deprivation.…”

Technical note: Extrapolation of hepatic glycogen concentration of the whole organ by performing a liver biopsy

“…Indeed, it has been repeatedly shown that liver glycogen concentration drastically decreases in early lactation (Weber et al, 2013(Weber et al, , 2015McCarthy et al, 2015), suggesting glycogenolysis. Recent manuscripts reporting hepatic concentrations of glycogen have aimed to evaluate the effects of different treatments or physiological conditions on liver glucose metabolism during the transition period and in early lactation (Hammon et al, 2009;Mann et al, 2018;Zenobi et al, 2018). Percutaneous needle liver biopsy was used in those studies, as it is the easiest way to obtain liver samples from live animals.…”