Methylglyoxal: A newly detected and potentially harmful metabolite in the blood of ketotic dairy cows

Abstract

Ketosis causes serious economic losses for the modern dairy industry because it is a highly prevalent metabolic disease among cows in high-producing herds during the transition period. Due to some striking similarities between diabetes in humans and ketosis in dairy cows, there is potential for the use of methylglyoxal (MGO)-commonly used in human diabetics-as a biomarker in dairy cattle. However, currently no data are available about the presence of MGO in the serum of dairy cattle or about the characteristics of its production or its potential contribution in the pathogenesis of ketosis. To determine the potential origin and pathway of formation of MGO, cows in different metabolic conditions [i.e., non-subclinically ketotic dairy cows in early lactation (n = 7), subclinically ketotic dairy cows in early lactation (n = 8), overconditioned dry cows (BCS >4.25, n = 6), and nonlactating heifers (n = 6)] were selected. Serum MGO concentrations were determined and correlated with indicators of the glucose and lipid metabolism and with haptoglobin (Hp) as an inflammatory marker. The serum MGO concentrations in subclinically ketotic cows (712.60 ± 278.77 nmol/L) were significantly greater than in nonlactating heifers (113.35 ± 38.90 nmol/L), overconditioned dry cows (259.71 ± 117.97 nmol/L), and non-subclinically ketotic cows (347.83 ± 63.56 nmol/L). In serum of lactating cows, concentrations of glucose and fructosamine were lower than in heifers and were negatively correlated with MGO concentrations. Even so, concentrations of metabolic and inflammatory markers such as dihydroxyacetone phosphate, nonesterified fatty acids, β-hydroxybutyrate, acetone, and Hp were remarkably higher in subclinically ketotic cows compared with nonlactating heifers; these metabolites were also positively correlated with MGO. In human diabetics elevated MGO concentrations are stated to originate from both hyperglycemia and the enhanced lipid metabolism, whereas higher MGO concentrations in subclinically ketotic cows were not associated with hyperglycemia. Therefore, our data suggest MGO in dairy cows to be a metabolite produced from the metabolization of acetone within the lipid metabolization pathway and from the metabolization of dihydroxyacetone phosphate. Furthermore, the highly positive correlation between MGO and Hp suggests that this reactive compound might be involved in the proinflammatory state of subclinical ketosis in dairy cows. However, more research is needed to determine the potential use of MGO as a biomarker for metabolic failure in dairy cows.