Precursors for liver gluconeogenesis in periparturient dairy cows

Abstract

The review is based on a compiled data set from studies quantifying liver release of glucose concomitant with uptake of amino acids (AA) and other glucogenic precursors in periparturient dairy cows. It has become dogma that AAs are significant contributors to liver gluconeogenesis in early lactation, presumably accounting for the observed lack of glucogenic precursors to balance estimated glucose need. Until recently, there has been paucity in quantitative data on liver nutrient metabolism in the periparturient period. Propionate is the quantitatively most important glucogenic precursor throughout the periparturient period. However, the immediate post partum increment in liver release of glucose is not followed by an equivalent increment in propionate uptake, because of the lower rate of increment in feed intake compared with the rate of increment in requirements for milk synthesis. The quantitative data on liver metabolism of AA do not support the hypothesis that the rapid post partum increase in net liver release of glucose is supported by increased utilisation of AA for gluconeogenesis. Only alanine is likely to contribute to liver release of glucose through its role in the inter-organ transfer of nitrogen from catabolised AA. AAs seem to be prioritised for anabolic purposes, indicating the relevance of investigating effects of supplying additional protein to post partum dairy cows. Combining data from quantitative and qualitative experimental techniques on L-lactate metabolism point to the conclusion that the quantitatively most important adaptation of metabolism to support the increased glucose demand in the immediate post partum period is endogenous recycling of glucogenic carbon through lactate. This is mediated by a dual site of adaptation of metabolism in the liver and in the peripheral tissues, where the liver affinity for L-lactate is increased and glucose metabolism in peripheral tissues is shifted towards L-lactate formation over complete oxidation.

049 Physiological and molecular mechanisms associated with performance, immunometabolic status, and liver function in transition dairy cows fed rumen-protected methionine or choline

“…It is also noteworthy that a reduction in net flux of carbon from volatile fatty acids across the liver and an increase in glucose release was detected early postpartum in a previous report (Larsen and Kristensen, 2013), indicating that the greatest flux through citric acid cycle occurs soon after parturition. Considering the severe negative energy balance and depressed DMI soon after parturition, the increased demand by the liver for energy and glucose synthesis likely accounted for such increase.…”

“…In terms of AA utilization, a previous study detected the greatest liver uptake of EAA at 4 d postpartum in dairy cows (Larsen and Kristensen, 2013). Similarly, hepatic uptake of total NEAA, especially Ala, also was substantially greater in the periparturient period, indicating this AA may act as a precursor for glucose synthesis (Kuhla et al, 2011, Larsen andKristensen, 2013).…”

“…Previous studies with dairy cattle proposed that AA profiles in serum are affected by a multitude of events such as skeletal muscle catabolism , Korhonen et al, 2002, dietary AA profile (Polan et al, 1991), liver gluconeogenesis, and gastrointestinal absorption (Meijer et al, 1995a). More recent data from a large number of studies revealed that the uptake of total non-essential amino acids by the liver was substantially greater in the peripaturient period (Kuhla et al, 2011, Larsen andKristensen, 2013). It has also been suggested that the liver may take up more AA from the circulation during the periparturient period for production of APP (Kurpad, 2006).…”

“…Around parturition, the demand for AA for glucose and protein synthesis increases abruptly and results in greatly increased AA uptake from the circulation (Larsen and Kristensen, 2013). The few published reports have revealed that circulating AA concentrations in dairy cows generally reach a nadir close to parturition mainly as a result of increased demand for milk protein synthesis and gluconeogenesis coupled with insufficient dietary intake (Verbeke et al, 1972, Meijer et al, 1995a, Doepel et al, 2002, Zhou et al, 2016d.…”

“…Similarly, hepatic uptake of total NEAA, especially Ala, also was substantially greater in the periparturient period, indicating this AA may act as a precursor for glucose synthesis (Kuhla et al, 2011, Larsen andKristensen, 2013). The greater (+4.10 kg/d more) milk yield in MET-supplemented cows at 4 d (Zhou et al, 2016g) (and Table 5.4) indicated that the greater uptake of these AA by mammary gland soon after parturition accounted for the lower AA concentration in the circulation compared with -10 d. Presumably, greater mammary availability of AA accounted for the greater milk protein % (Zhou et al, 2016g).…”