Normal glucose metabolism in carnivores overlaps with diabetes pathology in non-carnivores

Carnivores, such as the dolphin and the domestic cat, have numerous adaptations that befit consumption of diets with high protein and fat content, with little carbohydrate content. Consequently, nutrient metabolism in carnivorous species differs substantially from that of non-carnivores. Important metabolic pathways known to differ between carnivores and non-carnivores are implicated in the development of diabetes and insulin resistance in non-carnivores: (1) the hepatic glucokinase (GCK) pathway is absent in healthy carnivores yet GCK deficiency may result in diabetes in rodents and humans, (2) healthy dolphins and cats are prone to periods of fasting hyperglycemia and exhibit insulin resistance, both of which are risk factors for diabetes in non-carnivores. Similarly, carnivores develop naturally occurring diseases such as hemochromatosis, fatty liver, obesity, and diabetes that have strong parallels with the same disorders in humans. Understanding how evolution, environment, diet, and domestication may play a role with nutrient metabolism in the dolphin and cat may also be relevant to human diabetes

Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective

This Report has a number of inter-related general purposes. One is to explore the extent to which food, nutrition, physical activity, and body composition modify the risk of cancer, and to specify which factors are most important. To the extent that environmental factors such as food, nutrition, and physical activity influence the risk of cancer, it is a preventable disease. The Report specifies recommendations based on solid evidence which, when followed, will be expected to reduce the incidence of cancer

Evolution of placental function in mammals:the molecular basis of gas and nutrient transfer, hormone secretion, and immune responses

Placenta has a wide range of functions. Some are supported by novel genes that have evolved following gene duplication events while others require acquisition of gene expression by the trophoblast. Although not expressed in the placenta, high-affinity fetal hemoglobins play a key role in placental gas exchange. They evolved following duplications within the beta-globin gene family with convergent evolution occurring in ruminants and primates. In primates there was also an interesting rearrangement of a cassette of genes in relation to an upstream locus control region. Substrate transfer from mother to fetus is maintained by expression of classic sugar and amino acid transporters at the trophoblast microvillous and basal membranes. In contrast, placental peptide hormones have arisen largely by gene duplication, yielding for example chorionic gonadotropins from the luteinizing hormone gene and placental lactogens from the growth hormone and prolactin genes. There has been a remarkable degree of convergent evolution with placental lactogens emerging separately in the ruminant, rodent, and primate lineages and chorionic gonadotropins evolving separately in equids and higher primates. Finally, coevolution in the primate lineage of killer immunoglobulin-like receptors and human leukocyte antigens can be linked to the deep invasion of the uterus by trophoblast that is a characteristic feature of human placentation.</jats:p

Uric acid enhances longevity and endurance and protects the brain against ischemia

Among mammals, there is a positive correlation between serum uric acid (UA) levels and life span. Humans have high levels of UA because they lack a functional urate oxidase (UOX) enzyme that is present in shorter lived mammals. Here, we show that male and female mice with UOX haploinsufficiency exhibit an age-related elevation of UA levels, and that the life span of female but not male UOX+/− mice is significantly increased compared to wild-type mice. Serum UA levels are elevated in response to treadmill exercise in UOX+/− mice, but not wild-type mice, and the endurance of the UOX+/− mice is significantly greater than wild-type mice. UOX+/− mice exhibit elevated levels of brain-derived neurotrophic factor, reduced brain damage and improved functional outcome in a model of focal ischemic stroke. Levels of oxidative protein nitration and lipid peroxidation are reduced in muscle and brain tissues of UOX+/− mice under conditions of metabolic and oxidative stress (running in the case of muscle and ischemia in the case of the brain), consistent with prior evidence that UA can scavenge peroxynitrite and hydroxyl radical. Our findings reveal roles for UA in life span determination, endurance and adaptive responses to brain injury, and suggest novel approaches for protecting cells against injury and for optimizing physical performance.España, Ministerio de Educación, Cultura y Deporte EX2009–091

NON-INVASIVE MEASUREMENT OF OXIDATIVE STRESS IN SENIOR AND EXERCISING HORSES

The published data regarding oxidative stress in horses is generally concerned with blood and muscle samples. The aim of this thesis was to use non-invasive markers as a novel approach to investigate cellular stress in performance and senior horses. In addition, urine was analysed using IH NMR spectroscopy and renal insult during ageing and exercise was investigated using urinary N-acetyl-beta-D-glucosaminidase (NAG) activity. The results demonstrated that urinary thiobarbituric acid reactive substances (TBARS) in horses could be measured using a method adapted from Vagi (1976) and were significantly decreased following supplementation with antioxidants in the form of dandelion and milk thistle (p<O.05). Urinary TBARS were seen to decrease in horses supplemented with vitamin E at a level of 4mglkg bodyweight, but subsequently were unaffected in horses performing a sub-maximal exercise test on a treadmill when supplemented with vitamin E at a level of 3 mg/kg bodyweight. Urinary TBARS were seen to increase with age (P<O.05), consistent with increased lipid peroxidation in senior horses. Analysis using 1 H NMR spectroscopy revealed higher levels of aromatic amino acids in the urine of senior horses (p<O.05) and proteinuria quantification using the biuret assay demonstrated increased total proteinuria in the urine of senior horses compared to young horses (p<O.05). This indicated that subtle changes in renal, hepatic and endocrine functions may be evident in senior horses. TBARS in equine sweat could be measured using a method adapted from Vagi (1976) and were significantly decreased in horses performing a sub-maximal exercise test on a treadmill, following vitamin E supplementation (p<O.05). In addition, free radical scavenging activity of equine saliva could be measured using a method adapted from Atsumi et al (1999). Urinary NAG activity proved to be difficult to measure in the horse and may require further investigation to establish its potential use as a marker of renal insult in horses

The Role of Systemic Inflammation in the Development of Equine Laminitis

Laminitis is a crippling disease of horses that can result in chronic lameness and debilitation, and sometimes warrants euthanasia. It is a complication of inflammatory conditions such as gastrointestinal disease, and also occurs in obese, insulin-resistant horses with Equine Metabolic Syndrome (EMS). Inflammation and insulin resistance are risk factors for laminitis, and these mechanisms might converge to induce laminitis in susceptible animals. Systemic inflammation is often attributed to endotoxemia, although circulating endotoxin concentrations are not commonly measured in the clinical setting. Although a theoretic basis exists for endotoxemia in the pathogenesis of laminitis, administration of endotoxin alone does not induce the condition. This could be related to differences between experimental models and naturally occurring disease. Studies presented in this dissertation address the overall hypothesis that systemic inflammation causes laminitis and new experimental models can be developed to better represent clinical disease. Associations between systemic inflammation and laminitis were first established by measuring blood inflammatory cytokine expression during a laminitis induction model. A clinically relevant endotoxin model that induced laminitis was then sought, but endotoxin administration alone was insufficient to cause laminitis and endotoxin tolerance developed. Endotoxemia was therefore evaluated in conjunction with predisposing factors such as obesity. In horses with EMS, endotoxin infusion caused exaggerated inflammatory responses, and derangements in glucose homeostasis were more pronounced. Laminitis, however, did not develop. Repeated inflammatory events are implicated in the pathogenesis of sepsis-associated organ failure, so a final study was performed to test whether preexisting endotoxemia increased the risk of laminitis during subsequent carbohydrate overload-induced systemic inflammation. This did not occur, however systemic inflammation was more pronounced in horses that developed laminitis compared to non-responders, and tissues rather than circulating leukocytes appeared to be the major source of inflammatory mediators. Our results do not support a role for endotoxin as the causal agent of laminitis, even when combined with predisposing factors. Tissues appear to be an important source of inflammatory mediators, therefore their role in laminitis should be further characterized. Additionally, future investigations should determine whether exaggerated inflammatory responses and loss of glycemic control increase the risk of laminitis in horses with EMS

Relative value of certain economic traits and blood components as selection indices in beef cattle

Digitized 2007 AES.Includes bibliographical references (pages 36-39)

Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

Peer reviewedPublisher PD