Activity of hepatic but not skeletal muscle carnitine palmitoyltransferase enzyme is depressed by intravenous glucose infusions in lactating dairy cows*

Abstract

A positive energy balance in dairy cows pre-partum may decrease hepatic carnitine palmitoyltransferase (CPT) enzyme activity, which might contribute to disturbances of lipid metabolism post-partum. The purpose of this study was to investigate whether skeletal muscle CPT activity can also be downregulated during positive energy balance. Mid-lactating dairy cows were maintained on intravenous infusion of either saline (control) or glucose solutions that increased linearly over 24 days, remained at the 24-day level until day 28 and were suspended thereafter. Liver and skeletal muscle biopsies, as well as four diurnal blood samples, were taken on days 0, 8, 16, 24, and 32, representing infusion levels equivalent to 0%, 10%, 20%, 30% and 0% of the net energy for lactation (NE(L)) requirement respectively. Glucose infusion increased serum insulin concentrations on day 16 and 24 while plasma glucose levels were increased at only a single time point on day 24. Serum beta-hydroxybutyric acid concentrations decreased between day 8 and 24; whereas changes in non-esterified fatty acids were mostly insignificant. Total lipid contents of liver and skeletal muscle were not affected by treatment. Hepatic CPT activity decreased with glucose infusion (by 35% on day 24) and remained decreased on day 32. Hepatic expression levels of CPT-1A and CPT-2 mRNA were not significantly altered but tended to reflect the changes in enzyme activity. In contrast to the liver, no effect of glucose infusion was observed on skeletal muscle CPT activity. We conclude that suppression of CPT activity by positive energy balance appears to be specific for the liver in mid-lactating dairy cows.

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

“…In our study, the gene and protein expression of this enzyme was not affected by intravenous glucose or oral propylene glycol treatment. This is in accordance with the lack of difference in hepatic mitochondrial CPT activity measured in vitro and no change in the relative mRNA expression in hepatic CPT-1A after an 8-d infusion of intravenous glucose in an amount to supply 10% of the NE L requirements of mid-lactation cows (Al-Trad et al, 2010a).…”

“…Located on the outer mitochondrial membrane, CPT1A catalyzes the reaction of long-chain fatty acids with carnitine to a transportable form, an important step in determining the transport rate for β-oxidation (Al-Trad et al, 2010a). We found that the gene expression of CPT1A decreased in all groups in the first 4 d after enrollment, likely reflecting a physiological adaptation to a decreased hepatic uptake of circulating fatty acids after the peak of lipolysis at and immediately after calving.…”

Intravenous infusions of glucose stimulate key lipogenic enzymes in adipose tissue of dairy cows in a dose-dependent manner

“…As milk performance was completely unaffected by surplus glucose supply, we concluded that midlactation dairy cows on an energy-balanced diet directed any surplus of glucose predominantly to body fat reserves and not to increased lactation performance (Al-Trad et al, 2009). Total lipid content of the liver was also not affected (Al-Trad et al, 2010a), which supports the hypothesis that adipose tissue is the key player in lipogenesis during excessive glucose infusions. However, it remained unknown whether increased lipogenesis was simply the result of increased substrate availability or whether the enzymatic capacity of the lipogenic pathway increased in parallel.…”