Protein metabolism in response to metabolic acidosis in ruminants .

摘要

Use of readily fermentable diets in ruminant production systems is common practice at periods of high energy demand, such as at the onset of lactation. However, increased production and absorption of lactate and propionate can occur, resulting in a declining blood pH. This lower blood pH is a symptom of metabolic acidosis. In monogastrics, the physiologic buffering to counteract metabolic acidosis occurs via a whole body response, including increased skeletal muscle proteolysis, via the ubiquitin-mediated proteolytic pathway (UPP) after sarcomeric cleavage by caspase-3. Attenuation of proteolysis using exogenous supplementation of glutamine has been shown in monogastrics experiencing metabolic acidosis. However, whether the UPP is upregulated at the onset of metabolic acidosis in ruminants is unclear. In addition, it is unclear whether additional physiologic demands, such as the onset of lactation, could exacerbate the UPP response to metabolic acidosis. The objectives of the current research are to (1) examine regulation of the UPP at the onset of lactation in dairy cows, (2) examine protein degradation and amino acid response to varying severities of metabolic acidosis in ruminants, and (3) determine if glutamine supplementation provides a method for attenuation of proteolysis in ruminants during metabolic acidosis. The results presented in this thesis demonstrate that the onset of lactation does significantly upregulate mRNA expression of components of the UPP. However, induction of mild, moderate or a more severe acidosis did not upregulate the UPP in skeletal muscle. Induction of a severe metabolic acidosis instead downregulated mRNA expression of caspase-3 in slow-twitch skeletal muscle, in a muscle type specific manor, potentially providing an explanation as to the lack of regulation of the UPP during acidosis. Increased plasma glutamine in acidotic sheep also suggests that glutamine is not limiting in ruminants during acidosis, and no observed change in proteolytic components in response to glutamine supplementation in acidotic sheep further suggests that other regulatory amino acids could be more beneficial to ruminants with metabolic acidosis.