Cheng K.-K.,University of Cambridge |
Cheng K.-K.,University of Technology Malaysia |
Akasaki Y.,Boston University |
Akasaki Y.,Kagoshima University |
And 6 more authors.
Journal of Proteome Research | Year: 2015
Akt1 is a serine/threonine kinase that promotes cell growth and survival. Previously, Akt1 activation in a double transgenic (DTG) mouse model fed a high-fat/high-sucrose (HF/HS) diet was found to promote type IIb muscle growth and to lead to a significant reduction in obesity. Here, we have used metabolomics to examine the metabolic perturbations in blood serum and liver and gastrocnemius tissues of the DTG mice. Multivariate statistics highlighted consistent metabolic changes in gastrocnemius muscle following Akt1 activation, which included significant reductions of serine and histidine-containing dipeptides (anserine and carnosine), in addition to increased concentrations of phosphorylated sugars. In addition, Akt1-mediated regression in obesity could be associated with increased glycolysis in gastrocnemius muscle as well as increased gluconeogenesis, glycogenolysis, and ketogenesis in the liver. In old DTG animals, Akt1 activation was found to improve glucose metabolism and confer a beneficial effect in the regression of age-related fat accumulation. This study identifies metabolic changes induced by Akt1-mediated muscle growth and demonstrates a cross-talk between distant organs that leads to a regression of fat mass. The current findings indicate that agents that promote Akt1 induction in muscle have utility in the regression of obesity. © 2014 American Chemical Society.
Bryant M.,University of Leeds |
Ashton L.,University of Leeds |
Brown J.,University of Leeds |
Jebb S.,Medical Research Council MRC Human Nutrition Research |
And 3 more authors.
Health Technology Assessment | Year: 2014
Background: Lack of uniformity in outcome measures used in evaluations of childhood obesity treatment interventions can impede the ability to assess effectiveness and limits comparisons across trials. Objective: To identify and appraise outcome measures to produce a framework of recommended measures for use in evaluations of childhood obesity treatment interventions. Data sources: Eleven electronic databases were searched between August and December 2011, including MEDLINE; MEDLINE In-Process and Other Non-Indexed Citations; EMBASE; PsycINFO; Health Management Information Consortium (HMIC); Allied and Complementary Medicine Database (AMED); Global Health, Maternity and Infant Care (all Ovid); Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost); Science Citation Index (SCI) [Web of Science (WoS)]; and The Cochrane Library (Wiley) - from the date of inception, with no language restrictions. This was supported by review of relevant grey literature and trial databases. Review methods: Two searches were conducted to identify (1) outcome measures and corresponding citations used in published childhood obesity treatment evaluations and (2) manuscripts describing the development and/or evaluation of the outcome measures used in the childhood intervention obesity evaluations. Search 1 search strategy (review of trials) was modelled on elements of a review by Luttikhuis et al. (Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O'Malley C, Stolk RP, et al. Interventions for treating obesity in children. Cochrane Database Syst Rev 2009;1:CD001872). Search 2 strategy (methodology papers) was built on Terwee et al.'s search filter (Terwee CB, Jansma EP, Riphagen II, de Vet HCW. Development of a methodological PubMed search filter for finding studies on measurement properties of measurement instruments. Qual Life Res 2009;18:1115-23). Eligible papers were appraised for quality initially by the internal project team. This was followed by an external appraisal by expert collaborators in order to agree which outcome measures should be recommended for the Childhood obesity Outcomes Review (CoOR) outcome measures framework. Results: Three hundred and seventy-nine manuscripts describing 180 outcome measures met eligibility criteria. Appraisal of these resulted in the recommendation of 36 measures for the CoOR outcome measures framework. Recommended primary outcome measures were body mass index (BMI) and dual-energy X-ray absorptiometry (DXA). Experts did not advocate any self-reported measures where objective measurement was possible (e.g. physical activity). Physiological outcomes hold potential to be primary outcomes, as they are indicators of cardiovascular health, but without evidence of what constitutes a minimally importance difference they have remained as secondary outcomes (although the corresponding lack of evidence for BMI and DXA is acknowledged). No preference-based quality-of-life measures were identified that would enable economic evaluation via calculation of quality-adjusted life-years. Few measures reported evaluating responsiveness. Limitations: Proposed recommended measures are fit for use as outcome measures within studies that evaluate childhood obesity treatment evaluations specifically. These may or may not be suitable for other study designs, and some excluded measures may be more suitable in other study designs. Conclusions: The CoOR outcome measures framework provides clear guidance of recommended primary and secondary outcome measures. This will enhance comparability between treatment evaluations and ensure that appropriate measures are being used. Where possible, future work should focus on modification and evaluation of existing measures rather than development of tools de nova. In addition, it is recommended that a similar outcome measures framework is produced to support evaluation of adult obesity programmes. Funding: The National Institute for Health Research Health Technology Assessment programme. © Queen's Printer and Controller of HMSO 2014.
Jugdaohsingh R.,Medical Research Council MRC Human Nutrition Research |
Kessler K.,Medical Research Council MRC Human Nutrition Research |
Kessler K.,Medical University of Vienna |
Messner B.,Medical University of Vienna |
And 9 more authors.
Journal of Nutrition | Year: 2015
Background: Dietary silicon has been positively linked with vascular health and protection against atherosclerotic plaque formation, but the mechanism of action is unclear. Objectives: We investigated the effect of dietary silicon on 1) serum and aorta silicon concentrations, 2) the development of aortic lesions and serum lipid concentrations, and 3) the structural and biomechanic properties of the aorta. Methods: Two studies, of the same design, were conducted to address the above objectives. Female mice, lacking the apolipoprotein E (apoE) gene, and therefore susceptible to atherosclerosis, were separated into 3 groups of 10-15 mice, each exposed to a high-fat diet (21% wt milk fat and 1.5% wt cholesterol) but with differing concentrations of dietary silicon, namely: silicon-deprived (-Si; <3-μg silicon/g feed), silicon-replete in feed (+Si-feed; 100-μg silicon/g feed), and silicon-replete in drinking water (+Si-water; 115-μg silicon/mL) for 15-19 wk. Silicon supplementation was in the form of sodium metasilicate (feed) or monomethylsilanetriol (drinking water). Results: The serum silicon concentration in the -Si group was significantly lower than in the +Si-feed (by up to 78%; P < 0.003) and the +Si-water (by up to 84%; P < 0.006) groups. The aorta silicon concentration was also lower in the -Si group than in the +Si-feed group (by 65%; P = 0.025), but not compared with the +Si-water group. There were no differences in serum and aorta silicon concentrations between the silicon-replete groups. Body weights, tissue wet weights at necropsy, and structural, biomechanic, and morphologic properties of the aorta were not affected by dietary silicon; nor were the development of fatty lesions and serum lipid concentrations. Conclusions: These findings suggest that dietary silicon has no effect on atherosclerosis development and vascular health in the apoE mouse model of diet-induced atherosclerosis, contrary to the reported findings in the cholesterol-fed rabbit model. © 2015 American Society for Nutrition.
Schoenmakers I.,Medical Research Council MRC Human Nutrition Research |
Pettifor J.M.,University of Witwatersrand |
Pena-Rosas J.-P.,Evidence and Programme Guidance |
Lamberg-Allardt C.,University of Helsinki |
And 5 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2015
The Department of Nutrition for Health and Development of the World Health Organization (WHO) in collaboration with the Executive Committee of the 18th Vitamin D Workshop (VDW), organised a joint symposium on the prevention and consequences of vitamin D deficiency in pregnant women and children, convening experts on vitamin D, clinicians and policy-makers. The overall aim was to identify priority areas for research and to discuss the need for global options for policy, with a focus on the prevention of rickets in infants and children and vitamin D deficiency in pregnant women.The scope and purpose were: (i) to present the WHO research strategy for health, addressing vitamin D-related public health problems and the process for the development of evidence-informed guidelines in general and how vitamin D interventions in diverse populations could be prioritised; (ii) to provide an overview of vitamin D status in children and pregnant and lactating women across the world; (iii) to review the health risks associated with vitamin D deficiency in children and in pregnant women and their offspring; (iv) to understand the aetiology of vitamin D deficiency in pregnant women and children; (v) to identify and interpret biomarkers to assess vitamin D status and to consider possible clinical and biochemical screening tools for determining the prevalence of nutritional rickets in at risk groups or communities; and (vi) to provide an overview of policies and recommendations on vitamin D across the world. The format of the symposium was a composite of comprehensive scientific presentations and a panel debate with international experts on WHO guidelines, nutritional rickets, nutritional policy and consequences of vitamin D deficiency during pregnancy. This paper summarizes the content and outcomes of the panel debate. © 2015.
Braithwaite V.,Medical Research Council MRC Human Nutrition Research |
Jarjou L.M.A.,MRC Keneba |
Goldberg G.R.,Medical Research Council MRC Human Nutrition Research |
Prentice A.,Medical Research Council MRC Human Nutrition Research
Bone | Year: 2012
A relationship between iron and fibroblast growth factor-23 (FGF23) metabolic pathways has been proposed. Iron deficiency anaemia is prevalent in The Gambia and concentrations of fibroblast growth factor-23 FGF23 are elevated in a large percentage of Gambian children with rickets-like bone deformity.We speculate that low iron status may be involved in the aetiology of Gambian rickets. The aim of this study was to determine if there was a relationship between haemoglobin, as a marker of iron status, and FGF23 in samples from children with and without a history of rickets-like bone deformities in The Gambia. We conducted a retrospective analysis of studies carried out from 2006 to 2008 in children from a rural community in The Gambia where iron deficiency anaemia is endemic and where elevated circulating concentrations of FGF23 have been found. To investigate the relationship between circulating FGF23 and haemoglobin concentrations we used an age-adjusted linear regression model on data from children < 18. y of age with a family or personal history of rickets-like bone deformity (BD) (n= 108) and from the local community (LC) (n= 382).We found that circulating concentration of FGF23 was inversely correlated with haemoglobin concentration. This effect was more pronounced in BD children compared with LC children (interaction: P≤0.0001). Anaemia and elevated FGF23 were more prevalent in BD children compared to LC children (P=0.0003 and P=0.0001 respectively).In conclusion, there is a stronger relationship between FGF23 and haemoglobin in Gambian children with a history of rickets compared to local community children. This study provides support for the contention that iron may be involved in FGF23 metabolic pathways. © 2012 Elsevier Inc.