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Stevenson W.S.,University of Sydney | Hyland C.D.,Cancer and Haematology Division | Zhang J.-G.,Cancer and Haematology Division | Morgan P.O.,Cancer and Haematology Division | And 18 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

With the notable exception of humans, uric acid is degraded to (S)-allantoin in a biochemical pathway catalyzed by urate oxidase, 5-hydroxyisourate (HIU) hydrolase, and 2-oxo-4-hydroxy-4-carboxy-5- ureidoimidazoline decarboxylase inmost vertebrate species. A point mutation in the gene encoding mouse HIU hydrolase, Urah, that perturbed uric acid metabolism within the liver was discovered during a mutagenesis screen in mice. The predicted substitution of cysteine for tyrosine in a conserved helical region of the mutantencoded HIU hydrolase resulted in undetectable protein expression. Mice homozygous for this mutation developed elevated platelet counts secondary to excess thrombopoietin production and hepatomegaly. The majority of homozygous mutant mice also developed hepatocellular carcinoma, and tumor development was accelerated by exposure to radiation. The development of hepatomegaly and liver tumors in mice lacking Urah suggests that uric acid metabolites may be toxic and that urate oxidase activity without HIU hydrolase function may affect liver growth and transformation. The absence of HIU hydrolase in humans predicts slowed metabolism of HIU after clinical administration of exogenous urate oxidase in conditions of uric acid-related pathology. The data suggest that prolonged urate oxidase therapy should be combined with careful assessment of toxicity associated with extrahepatic production of uric acid metabolites. Source


Krezel M.A.,University of Melbourne | Rezmann L.A.,University of Melbourne | Varghayee N.,University of Melbourne | Pete J.,Baker International Diabetes Institute | And 2 more authors.
Bioscience, Biotechnology and Biochemistry | Year: 2011

To investigate the expression of the unknown angiotensin II type 2 receptor interacting protein (ATIP) isoforms in the rat we used the known sequences of human and mouse ATIP to design sequencing primers to enable us to sequence rat ATIP3 and ATIP4. Exon 4, which is present in human but not mouse ATIP, was not identified in the coding region of rat ATIP. The expression levels of these genes in a range of rat tissues were examined, and we concluded that there is little similarity in the relative tissue distribution of the various ATIP isoforms in rat and human. Source


Backholer K.,Monash University | Walls H.L.,Monash University | Magliano D.J.,Monash University | Magliano D.J.,Baker International Diabetes Institute | Peeters A.,Monash University
American Journal of Public Health | Year: 2010

In 2008, The Council of Australian Governments set a target to increase by 5% the proportion of Australian adults at a healthy body weight by 2017, over a 2009 baseline. Target setting is a critical component of public health policy for obesity prevention; however, there is currently no context within which to choose such targets. We analyzed the changes in current weight gain that would be required to meet Australian targets. By using transition-based multistate life tables to project obesity prevalence, we found that meeting national healthy weight targets by 2017 will require a 75% reduction in current 5-yearweight gain. A reliable model of future body weight prevalence is critical to set, evaluate, and monitor national obesity targets. Source


Egger G.,Southern Cross University of Australia | Egger G.,Center for Health Promotion and Research | Dixon J.,Baker International Diabetes Institute
Obesity Reviews | Year: 2011

A form of low-grade, systemic inflammation ('metaflammation') is linked to many types of chronic disease. Initially, this was thought to be causally related to weight gain and obesity and a possible explanation of the link between obesity and disease. However, several lifestyle-related inducers of such inflammation, some of which are associated with obesity, but some of which are not, have now been identified. The most common of these have been nutritive related, suggesting that there could still be a relationship, either directly or indirectly, with obesity. Here we provide evidence for non-nutritive inflammatory inducers, providing further support for an earlier suggestion that while obesity, beyond a point, may have a direct link with disease, this may be neither necessary nor sufficient to explain the current epidemic of chronic disease. A more ubiquitous cause encompassing all inflammatory inducers is the modern, post-industrial environment and lifestyles emanating from this. Obesity may thus be more of 'a canary in the mineshaft', warning of bigger global problems, than just a single pathway to modern environmentally driven disease. © 2010 The Authors. obesity reviews © 2010 International Association for the Study of Obesity. Source


Ryan A.T.,University of Adelaide | Feinle-Bisset C.,University of Adelaide | Kallas A.,University of Adelaide | Wishart J.M.,University of Adelaide | And 3 more authors.
American Journal of Clinical Nutrition | Year: 2012

Background: Intraduodenal fat and carbohydrate modulate antropyloroduodenal motility and hormone release and suppress appetite and energy intake in a load-dependent manner. Protein also suppresses energy intake, but its effects on these gastrointestinal factors and their role in the appetite-suppressive effects of protein remain unclear. Objective: We aimed to characterize the effects of different intraduodenal protein loads on antropyloroduodenal pressures, gastrointestinal hormone release, glucose and insulin concentrations, appetite perceptions, and energy intake. Design: Sixteen lean, healthy men were studied on 4 occasions in a randomized, double-blind fashion. Antropyloroduodenal pressures, plasma glucagon-like peptide 1 (GLP-1), cholecystokinin, peptide YY, ghrelin, blood glucose, serum insulin, and appetite were measured during 60-min, 4-mL/min intraduodenal infusions of protein at 0.5, 1.5, or 3 kcal/min or saline (control). Energy intakes at a buffet lunch consumed immediately after the infusion were quantified. Results: Increases in the load of protein resulted in greater suppression of antral motility, greater stimulation of basal and isolated pyloric pressures and plasma cholecystokinin and GLP-1 concentrations, and greater suppression of energy intake. However, energy intake was reduced only after a protein load of 3 kcal/min compared with after all other treatments (P < 0.05). The suppression of energy intake after adjustment for cholecystokinin, GLP-1, and insulin was related inversely with basal pyloric pressure (r = 20.51, P < 0.001). Conclusion: The acute effects of intraduodenal protein on antropyloroduodenal motility, gastrointestinal hormone release, glucose, and insulin are load dependent and contribute to the suppression of energy intake. This trial was registered at www.anzctr.org.au as 12610000376044. © 2012 American Society for Nutrition. Source

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