1. The aim of the study was to investigate the effects of feeding fast growing turkeys with differentiated dietary calcium (Ca) content, and the partial replacement of vitamin D-3 in the feed with 25-hydroxycholecalciferol (25(OH)D-3), on skeletal properties.2. One-day-old Big-6 male turkeys (n = 1008) were randomly divided into 4 groups, and two subgroups were created within each group. The groups were differentiated with 4 levels of Ca provision in the feed, namely 85% of the National Research Council (NRC) recommendation (Group Ca-1); 95% as above (Group Ca-2); 105% as above (Group Ca-3); and 115% as above (Group Ca-4). The first subgroup received the recommended dosage of cholecalciferol (vitamin D-3 subgroup) in the feed, while in the second subgroup (Hy-D subgroup), half of the dosage of cholecalciferol was replaced with 25(OH)D-3. At the ages of 4, 8, 12 and 20 weeks, 7 turkeys from each subgroup were randomly selected and killed to obtain the right tibia for densitometric, geometric and mechanical analyses.3. This study showed advantageous effects of increased calcium supply in the diet on skeletal system properties, that were increased and produced the most desirable traits in turkeys receiving 95%, 105% and 115% of the NRC calcium recommendation. Benefits resulting from administration of 25(OH)D-3 in the diet were also obtained in the skeletal formation of turkeys, and the most advantageous effects were present in the group receiving 105% of recommended dietary Ca.4. Effects on the metabolic response of the skeleton of turkeys to manipulation of dietary calcium content and vitamin D-3 source were the most evident in the groups between 4 and 12 weeks of life, and demonstrated a limited ability to induce a positive influence on bone properties at advanced stages of the production cycle by alteration of these dietary factors.

The mitochondrial citrate transport protein (CTP), encoded by SLC25A1, accommodates bidirectional trafficking of citrate between the mitochondria and cytosol, supporting lipid biosynthesis and redox homeostasis. Genetic CTP deficiency causes a fatal neurodevelopmental syndrome associated with the accumulation of L- and D-2-hydroxyglutaric acid, and elevated CTP expression is associated with poor prognosis in several types of cancer, emphasizing the importance of this transporter in multiple human pathologies. Here we describe the metabolic consequences of CTP deficiency in cancer cells. As expected from the phenotype of CTP-deficient humans, somatic CTP loss in cancer cells induces broad dysregulation of mitochondrial metabolism, resulting in accumulation of lactate and of the L- and D- enantiomers of 2-hydroxyglutarate (2HG) and depletion of TCA cycle intermediates. It also eliminates mitochondrial import of citrate from the cytosol. To quantify the impact of CTP deficiency on metabolic flux, cells were cultured with a set of 13C-glucose and 13C-glutamine tracers with resulting data integrated by metabolic flux analysis (MFA). CTP-deficient cells displayed a major restructuring of central carbon metabolism, including suppression of pyruvate dehydrogenase (PDH) and induction of glucose-dependent anaplerosis through pyruvate carboxylase (PC). We also observed an unusual lipogenic pathway in which carbon from glucose supplies mitochondrial production of alpha-ketoglutarate (AKG), which is then trafficked to the cytosol and used to supply reductive carboxylation by isocitrate dehydrogenase 1 (IDH1). The resulting citrate is cleaved to produce lipogenic acetyl-CoA, thereby completing a novel pathway of glucose-dependent reductive carboxylation. In CTP deficient cells, IDH1 inhibition suppresses lipogenesis from either glucose or glutamine, implicating IDH1 as a required component of fatty acid synthesis in states of CTP deficiency.

Objective: The aim of the study was to test the hypothesis that oral administration with 3-hydroxy-3-methylbutyrate (HMB) positively influences bone metabolism and diminishes fundectomy-induced osteopenia of the axial skeleton in pigs. The pig model was chosen because of its recognized physiologic and anatomic similarities of the gastrointestinal tract and skeletal system to those of humans.Methods: Eighteen male pigs were divided into three weight-matched groups at 40 d of life. Animals from the first and second groups were subjected to experimental fundectomy and the third group was sham operated. Starting the day after the fundectomy, the first and second groups received placebo and HMB, respectively. Animals were sacrificed at the age of 8 mo to obtain L-5 and L-6 vertebrae for analysis. The effects of HMB administration on plasma amino acids concentrations, bone mineral density, morphology, and mechanical properties of the lumbar vertebrae were determined.Results: The HMB treatment increased the weight of the vertebrae, bone mineral density, bone mineral content, total bone volume, trabecular bone mineral density, mean volumetric bone mineral density, calcium hydroxyapatite density in the trabecular and cortical bones, and plasma amino acid concentrations in the fundectomized pigs (P < 0.05). Mechanical strength of the spine, expressed by the values of ultimate force, Young's modulus, ultimate stress, stiffness, and work to the ultimate force point was increased in HMB-treated pigs (P < 0.05).Conclusion: HMB administration to fundectomized pigs improved plasma amino acids concentrations and diminished development of fundectomy-induced osteopenia of the axial skeleton. (C) 2008 Elsevier Inc. All rights reserved.

Background. The effect of dexamethasone (Dex) on postnatal bone formation processes is known to decrease the synthesis of collagen and bone matrix, but the effect of alpha-ketoglutarate (AKG) is to induce positive effects on growth and skeletal development during postnatal life. However, the effects of Dex and AKG treatment on the prenatal processes of skeletal development have not been investigated so far.Objective. The aim of this study was to determine the effect of Dex and AKG administered separately or simultaneously to sows during the last three weeks of pregnancy on the skeletal development in fetuses.Methods. Immediately after birth blood samples were collected from non-suckling piglets for alkaline phosphatase and osteocalcin determinations, and the humeri were isolated. Bone mineral density (BMD) and bone mineral content (BMC) of humeri and the geometric and mechanical properties were evaluated.Results. Dex and AKG administered separately to pregnant sows during the last 24 days of prenatal life decreased BMD, BMC, and geometric and mechanical parameters of humeri in the newborns. Simultaneous administration of Dex and AKG significantly increased the analyzed properties of humeri.Conclusion. The bone mineral density and mechanical and geometric properties of humeri indicate an inverse effect of maternal separate or simultaneous administration of AKG and Dex to sows on bone development during the last 24 days of prenatal life.

Summary Glucocorticoids play an important role in general growth and the maintenance of bone mass in the skeleton. Steroid therapy induces bone loss and influences the transcription of some regulatory factors determining the ratio of bone turnover. Glucocorticoids increase bone resorption and decrease bone formation which leads to diminishing bone mass and bone mineral density. Osteoporosis is globally one of the most common metabolic bone diseases, and has increasingly been recognized as being a major public health issue. Glucocorticoids increase the risk of rib and limb bone fractures by modifying and decreasing bone quality. Glucocorticoids are very often used as anti-inflammatory and immunosuppressive drugs for serious rheumatoid arthritis and other systemic diseases in large groups of young children, and Glucocorticoids therapy is also used for children and youth having asthma as well as being administered during pregnancy in order to improve lung morphology in premature fetuses. No glucocorticoid drugs which would act without negative side effects are currently available. This review presents the mechanisms of glucocorticoid action based on the latest research and newest factors controlling bone remodeling such as osteoprotegerin and osteoprotegerin-ligands.

The aim of the study was to establish the influence of dexamethasone and alpha-ketoglutarate administration to pregnant sows on the prenatal programming of the growth hormone level, cortisol, insulin and IGF-I in the blood serum of newborn piglets assessed just after their birth and prior to suckling. The foetal development is dependent on and determined by hormones such as glucocorticoids as well as nutrient supply through the sow, especially from the digestive tract. All these factors determine pre- and neonatal growth. The experiment was conducted over the final 24 days of pregnancy in sows treated i.m. with dexamethasone at a dose of 3 mg per sow every second day or alpha-ketoglutarate administered orally daily at a dose of 0.4 g/kg b.w. The blood samples were collected from the subclavian vein of un-suckled piglets immediately following their birth and were centrifuged straight away and the serum stored at -25 degrees C until further analysis. Hormone concentrations were determined using ELISA kit. The obtained results indicate that maternal administration of dexamethasone increased the level of cortisol while alpha-ketoglutarate increased the levels of cortisol and IGF I whereas simultaneous administration of dexamethasone and AKG significantly increased the growth hormone. These results of separate or simultaneous maternal administration of dexamethasone and alpha-ketogluta rate during the last 24 days of pregnancy indicated the activation of different mechanisms and different prenatal effects on the levels of cortisol, growth hormone and IGF I in serum assessed immediately following the birth of the piglets.

The aim of this study was to determine the influence of daily oral administration of alpha-ketoglutarate (AKG) on bone mineral density of the femur and concentration of 17-beta-oestradiol in blood plasma during 70 d of postnatal life in piglets. All the animals were kept under standard rearing conditions. AKG was administered orally from the 1(st) d of life, while the control piglets were treated in the same way and time with physiological saline. The experimental and control groups were assigned to 6 age subgroups: 3, 14, 21, 35, 56 and 70 d of life. The animals from both groups were euthanised, then bone samples were collected and frozen at -25 degrees C until further analyses. Using dual-energy x-ray absorptiometry (DEXA method) bone mineral density of the femora was estimated. Additionally, 17-beta-oestradiol concentration in blood plasma was assayed using RIA-test. The obtained results indicate positive influence of enteral AKG administration on bone mineral density of the femur in piglets. Moreover, AKG increased the level of 17-beta-oestradiol in blood plasma in post-weaned piglets.