Increased Pyruvate Dehydrogenase Activity in Skeletal Muscle of Growth Restricted Ovine Fetuses.

Increased Pyruvate Dehydrogenase Activity in Skeletal Muscle of Growth Restricted Ovine Fetuses. Am J Physiol Regul Integr Comp Physiol. 2019 Jul 17;: Authors: Pendleton AL, Humphreys LR, Davis MA, Camacho LE, Anderson MJ, Limesand SW Abstract Fetal sheep with placental insufficiency-induced intrauterine growth restriction (IUGR) have lower fractional rates of glucose oxidation and greater gluconeogenesis, indicating lactate shuttling between skeletal muscle and liver. Suppression of pyruvate dehydrogenase (PDH) activity was proposed because of greater pyruvate dehydrogenase kinase 4 (PDK4) and pyruvate dehydrogenase kinase 1 (PDK1) mRNA concentrations in IUGR muscle. Although PDK1 and PDK4 inhibit PDH activity to reduce pyruvate metabolism, PDH protein concentrations and activity have not been examined IUGR fetal skeletal muscle. Therefore, we evaluated the protein concentrations and activity of PDH and the kinases and phosphatases that regulate PDH phosphorylation in the semitendinosus muscle from placenta insufficiency-induced IUGR sheep fetuses and control fetuses. Immunoblots were performed for PDH, phosphorylated PDH (E1α), PDK1, PDK4, pyruvate dehydrogenase phosphatase 1 and 2 (PDP1 and PDP2). Additionally, the PDH, lactate dehydrogenase (LDH), and citrate synthase (CS) enzymatic activities were measured. Phosphorylated PDH concentrations were 28% lower (P<0.01), and PDH activity was 67% greater (p<0.01), in IUGR fetal ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research