2007 Annual Report
T cell Accumulation in Adipose Tissue: The molecular mechanism responsible for the inflammatory response in diet-induced obesity is not completely understood. Children's Nutrition Research Center researchers documented for the first time that white blood cells accumulated in fat tissue of obese individuals. Additionally, researchers identified a protein that is capable of attracting these cells to fat tissue. Researchers analyzed cell types and proteins in adipose tissue in an animal model (mice fed a diet high in saturated fatty acids) and in human biopsy tissue (humans with morbid obesity and the metabolic syndrome). The outcome of this work will be very important since it is the first step in analyzing the contributions of the immune system in adipose tissue, and it provides another marker for the early detection of systemic inflammation in obesity. [NP107, Component 6 Prevention of Obesity & Disease] (CNRC Project 4)
ICAM-1 and Activated Macrophages in Adipose Tissue: Identifying the molecular mechanism responsible for the inflammatory response in diet-induced obesity is needed. Scientists at the Children's Nutrition Research Center documented activated macrophages in fat tissue in diet-induced obesity, and identified an important marker for inflammation in the tissue. TResearchers analyzed adipose tissue and blood in an animal model (mice fed a diet rich in saturated fatty acids). The impact of this work is very significant since it represents the recognition of a second white blood cell type in fat inflammation and the occurrence of a key marker. [NP107, Component 6 Prevention of Obesity & Disease] (CNRC Project 4)
Identification of Clock-Regulated Genes within the Adipocyte: Through our experiments, Children's Nutrition Research Center scientists identified the clock-regulated genes within the fat cell. Genes within pathways related to transport, transcription, development, cell cycle, metabolism, cell division, and in particular, lipid biosynthesis were found to be altered in adipocyte-specific dominant negative CLOCK mutant (ACM) mice. Many of these genes were not known to be regulated by the circadian clock (internal body clock) prior to these experiments. Genes related to lipogenesis, or the production of lipids, were all elevated at the transition from sleeping to waking in the transgenic animals, indicating increased potential for fat formation during this time period. These findings suggest that the nutrient makeup of the diet and timing of feeding may both impact and/or be impacted by disruptions in normal patterns of circadian rhythms. [NP107, Component 6 Prevention of Obesity & Disease] (CNRC Project 6)
Characterization of an Adipocyte-Specific CLOCK Mutant Animal Model: Scientists at the Children's Nutrition Research Center, Houston, TX ,established a transgenic colony of adipocyte-specific dominant negative CLOCK mutant (ACM) mice. The ACM animal model is the first model with a specific disruption of the circadian clock only within the fat cell. While other animal models with a global loss of the circadian clock have been reported to develop obesity and associated co-morbidities, both behavior and metabolism are altered in these ubiquitously disrupted animals, and it is not known whether the development of obesity in these animals is due to behavioral changes or direct alterations by the circadian clock. Through the use of the ACM animal model, we will be able to understand the means by which alterations in circadian patterns of metabolism and gene expression can lead to obesity. [NP107, Component 6 Prevention of Obesity & Disease] (CNRC Project 6)
Assessing DXA Software for Improved Accuracy: In order to accurately calculate body composition measurements in children, additional assessment of the dual energy X-ray absorptiometry (DXA) tool and related software is needed. Our independent assessment of the newest software changes for DXA scans in children have shown that body fat values are increased for all children weighing less than 40 kg, compared with older software once used. Therefore, children examined in 2007 could appear to have increased body fatness compared with children of the same weight from only a few years ago. This software effect may contribute to a false perception that children are continuing to get fatter, which is important to recognize in nutrition-related research. Most importantly, a more accurate tool can be utilized for future research in children. [NP107, Component 6 Prevention of Obesity & Disease] (CNRC Project 2)
Ellis, K.J., Yao, M., Shypailo, R.J., Urlando, A., Wong, W.W., Heird, W.C. 2007. Body-composition assessment in infancy: Air-displacement plethysmography compared with a reference 4-compartment model. American Journal of Clinical Nutrition. 85(1):90-95.
Ellis, K.J. 2007. Evaluation of body composition in neonates and infants. Seminars in Fetal & Neonatal Medicine. 12(1):87-91.
D'Amico, S., Shi, J., Sekhar, R.V., Jahoor, F., Ellis, K.J., Rehman, K., Willis, J., Maldonado, M., Balasubramanyam, A. 2006. Physiologic growth hormone replacement improves fasting lipid kinetics in patients with HIV lipodystrophy syndrome. American Journal of Clinical Nutrition. 84(1):204-211.
Liew, G., Shankar, A., Wang, J.J., Klein, R., Bray, M.S., Couper, D.J., Wong, T.Y. 2006. Apolipoprotein E gene polymorphisms are not associated with diabetic retinopathy: The atherosclerosis risk in communities study. American Journal of Opthalmology. 142:105-111.
Lee, C.R., North, K.E., Bray, M.S., Fornage, M., Seubert, J.M., Newman, J.W., Hammock, B.D., Couper, D.J., Heiss, G., Zeldin, D.C. 2006. Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study. Human Molecular Genetics. 15(10):1640-1649.
Soliman, P.T., Wu, D., Tortolero-Luna, G., Schmeler, K.M., Slomovitz, B.M., Bray, M.S., Gershenson, D.M., Lu, K.H. 2006. Association between adiponectin, insulin resistance, and endometrial cancer. Cancer. 106:2376-2381.
Durgan, D.J., Trexler, N.A., Egbejimi, O., McElfresh, T.A., Suk, H.Y., Petterson, L.E., Shaw, C.A., Hardin, P.E., Bray, M., Chandler, M.P., Chow, C., Young, M.E. 2006. The circadian clock within the cardiomyocyte is essential for responsiveness of the heart to fatty acids. Journal of Biological Chemistry. 281(34):24254-24269.
Li, Z., Rumbaut, R.E., Burns, A.R., Smith, C.W. 2006. Platelet response to corneal abrasion is necessary for acute inflammation and efficient re-epithelialization. Investigative Opthalmology and Visual Science. 47:4794-4802.
Hertel, P.M., Chacko, S.K., Pal, S., Sunehag, A.L., Haymond, M.W. 2006. Subcutaneous infusion and capillary "finger stick" sampling of stable isotope tracer in metabolic studies. Pediatric Research. 60(5):597-601.
Hays, S.P., Smith, E.O., Sunehag, A.L. 2006. Hyperglycemia is a risk factor for early death and morbidity in extremely low birth-weight infants. Pediatrics. 118:1811-1818.
Tyler, C., Johnston, C.A., Madhukar, M., Foreyt, J.P. 2005. Practical strategies for treating obesity in Mexican Americans. Obesity Management. 1(6):247-250.
Sunehag, A.L., Haymond, M.W. 2006. Methods of measuring nutrient substrate utilization using stable isotopes. In: Thureen, P., Hay W., Jr., editors. Neonatal Nutrition and Metabolism. 2nd Edition. Cambridge: Cambridge University Press. p. 617-630.
Motil, K.J. 2006. Peptic ulcer disease. In: McMillian, J.A., Feigin, R.D., DeAngelis, C.D., Jones, M.D., editors. Oski's Pediatrics: Principles and Practice of Pediatrics. 4th edition. Philadelphia, PA: Lippincott Williams & Wilkins. p. 1932-1937.
Motil, K.J., Phillips, S.M., Conkin, C. 2006. Nutritional assessment. In: Wyllie, R., Hyams, J.S., Kay, M. editors. Pediatric Gastrointestinal and Liver Disease. 3rd edition. London, UK: Elsevier. p. 1095-1111.
Wong, T.Y., Shankar, A., Klein, R., Bray, M.S., Couper, D.J., Klein, B.E.K., Sharrett, R.A., Folsom, A.R. 2006. Apolipoprotein E gene and early age-related maculopathy. Opthalmology. 114(2):255-259.
Heck, A.L., Bray, M.S., Scott, A., Blanton, S.H., Hecht, J.T. 2005. Variation in CASP10 gene is associated with idiopathic talipes equinovarus. Journal of Pediatric Orthopaedics. 25(5):598-602.
Hardin, D.S., Rice, J., Cohen, R.C., Ellis, K.J., Nick, J.A. 2005. The metabolic effects of pregnancy in cystic fibrosis. American Journal of Obstetrics and Gynecology. 106(2):367-375.
Durgan, D.J., Hotze, M.A., Tomlin, T.M., Egbejimi, O., Graveleau, C., Abel, E.D., Shaw, C.A., Bray, M.S., Hardin, P.E., Young, M.E. 2005. The intrinsic circadian clock within the cardiomyocyte. American Journal of Physiology - Heart and Circulatory Physiology. 289:H1530-H1541.
Fornage, M., Lee, C.R., Doris, P.A., Bray, M.S., Heiss, G., Zeldin, D.C., Boerwinkle, E. 2005. The soluble epoxide hydrolase gene harbors sequence variations associated with susceptibility to and protection from incident ischemic stroke. Human Molecular Genetics. 14(19):2829-2837.
Brake, D.K., Smith, E.O., Mersmann, H.J., Smith, C.W., Robker, R.L. 2006. ICAM-1 expression in adipose tissue: Effects of diet-induced obesity in mice. American Journal of Physiology Cell Physiology. 291(6):C1232-1239.
Tyler, C., Johnston, C.A., Fullerton, G., Foreyt, J.P. 2007. Reduced quality of life in very overweight Mexican American adolescents. Journal of Adolescent Health. 40(4):366-368.
Johnston, C.A., Steele, R.G. 2007. Treatment of pediatric overweight: an examination of feasibility and effectiveness in an applied clinical setting. Journal of Pediatric Psychology. 32(1):106-110.
Foreyt, J.P. 2006. The role of lifestyle modification in dysmetabolic syndrome management. In: Bantle, J.P., Slama, G., editors. Nutritional Management of Diabetes Mellitus and Dysmetabolic Syndrome. Basel: Karger Publishers. p. 197-206.
Espeland, M.A., Dotson, K., Jaramillo, S.A., Kahn, S.E., Harrison, B., Montez, M., Foreyt, J.P., Montgomery, B., Knowler, W.C. 2006. Consent for genetics studies among clinical trial participants: Findings from Action for Health in Diabetes (Look AHEAD). Clinical Trials. 3(5):443-456.
Butte, N.F., Cai, G., Cole, S.A., Wilson, T.A., Fisher, J.O., Zakeri, I.F., Ellis, K.J., Comuzzie, A.G. 2007. Metabolic and behavioral predictors of weight gain in Hispanic children: The Viva la Familia Study. American Journal of Clinical Nutrition. 85(6):1478-1485.
Bray, M.S., Young, M.E. 2006. Circadian rhythms in the development of obesity: Potential role for the circadian clock within the adipocyte. Obesity Reviews. 8(2):169-181.
Wu, H., Ghosh, S., Perrard, X.D., Feng, L., Garcia, G.E., Perrard, J.L., Sweeney, J.F., Peterson, L.E., Chan, L., Smith, C.W., Ballantyne, C.M. 2007. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation. 115(80):1029-1038.
Tejero, M.E., Cai, G., Goring, H.H.H., Diego, V., Cole, S.A., Bacino, C.A., Butte, N.F., Comuzzie, A.G. 2007. Linkage analysis of circulating levels of adiponectin in Hispanic children. International Journal of Obesity. 31(3):535-542.
Ferdinands, J.M., Mannino, D.M., Gwinn, M.L., Bray, M.S. 2007. ADRB2 Arg16Gly polymorphism, lung function, and mortality: Results from the atherosclerosis risk in communities study. PLoS One. 2(3):e289.
Cai, G., Cole, S.A., Haack, K., Butte, N.F., Comuzzie, A.G. 2007. Bivariate linkage confirms genetic contribution to fetal origins of childhood growth and cardiovascular disease risk in Hispanic children. Human Genetics. 121(6):737-744.
Butte, N.F., Garza, C., De Onis, M. 2007. Evaluation of the feasibility of international growth standards for school-aged children and adolescents. Journal of Nutrition. 137(1):153-157.
Butte, N.F., Garza, C., De Onis, M. 2006. Evaluation of the feasibility of international growth standards for school-aged children and adolescents. Food and Nutrition Bulletin. 27(4):S169-S174.
Grove, M.L., Morrison, A., Folsom, A.R., Boerwinkle, E., Hoelscher, D.M., Bray, M.S. 2007. Gene-environment interaction and the GNB3 gene in the Atherosclerosis risk in communities study. International Journal of Obesity. 31(6):919-926.
Seminara, D., Khoury, M.J., O'Brien, T.R., Manolio, T., Gwinn, M.L., Little, J., Higgins, J.T., Bernstein, J.L., Boffetta, P., Bondy, M., Bray, M.S., Brenchley, P.E., Buffler, P.A., Casas, J.P., Chokkalingam, A.P., Danesh, J., Smith, G.D., Dolan, S., Duncan, R., Gruis, N.A., Hashibe, M., Hunter, D., Jarvelin, M., Malmer, B., Maraganore, D.M., Newton-Bishop, J.A., Riboli, E., Salanti, G., Taioli, E., Timpson, N., Uitterlinden, A.G., Vineis, P., Vareham, N., Winn, D.M., Zimmern, R., Ioannidis, J.P.A., for the Human Genome Epidemiology Network and the Network of Investigator Networks. 2007. The emergence of networks in human genome epidemiology: Challenges and opportunities. Epidemiology. 18(1):1-8.
Poston, W.S.C., Haddock, C.K., Pinkston, M.M., Pace, P., Reeves, R.S., Karakoc, N., Jones, P., Foreyt, J.P. 2006. Evaluation of a primary care-oriented brief counselling intervention for obesity with and without orlistat. Journal of Internal Medicine. 260:388-398.
Voruganti, V.S., Goring, H.H., Diego, V.P., Cai, G., Mehta, N.R., Haack, K., Cole, S.A., Butte, N.F., Comuzzie, A.G. 2007. Genome-wide scan for serum ghrelin detects linkage on chromosome 1p36 in Hispanic children: Results from the Viva la Familia study. Pediatric Research. 62(4):445-450.
Rankinen, T., Bray, M.S., Hagberg, J.M., Perusse, L., Roth, S.M., Wolfarth, B., Bourchard, C. 2006. The human gene map for performance and health-related fitness phenotypes: The 2005 update. Medicine and Science in Sports and Exercise. 38(11):1863-1888.
Lee, C.R., North, K.E., Bray, M.S., Avery, C.L., Mosher, M.J., Couper, D.J., Coresh, J., Folsom, A.R., Boerwinkle, E., Heiss, G., Zeldin, D.C. 2006. NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: The atherosclerosis risk in communities study. Pharmacogenetics and Genomics. 16(12):891-899.
White, J.S., Foreyt, J. 2006. Ten myths about high-fructose corn syrup. Food Technology. 60(10):96.
Ellis, K.J., Grund, B., Visnegarwala, F., Thackeray, L., Miller, C.G., Chesson, C.E., El-Sadr, W., Carr, A. 2007. Visceral and subcutaneous adiposity measurements in adults: Influence of measurement site. Obesity. 15:1441-1447.
Motil, K.J. 2006. Necrotizing enterocolitis. In: McMillian, J.A., Feigin, R.D., DeAngelis, C.D., Jones, M.D., editors. Oski's Pediatrics: Principles and Practice of Pediatrics. 4th edition. Philadelphia, PA: Lippincott Williams & Wilkins. p. 389-397.
Quiros-Tejeira, R.E., Rivera, C.A., Ziba, T.T., Mehta, N., Smith, C.W., Butte, N.F. 2007. Risk for nonalcoholic fatty liver disease in Hispanic Youth with BMI > or = 95th percentile. Journal of Pediatric Gastroenterology and Nutrition. 44(2):228-236.
Oyafemi, O.M., Ellis, K.J., Griffin, I.J., Abrams, S.A. 2005. Bone mineral status asessment by ultrasound in preterm infants. International Journal of Body Composition Research. 3(4):141-145.
Shypailo, R.J., Ellis, K.J. 2005. Bone assessment in children: Comparison of fan-beam dxa analysis. Journal of Clinical Densitometry. 4(8):445-453
Butte, N.F. 2005. Energy requirements during pregnancy and consequences of deviations from requirement on fetal outcome. In: Vevey, S., Karger, A.G., editors. Nestle Nutrition Workshop Series Pediatric Program. Basel, Switzerland: Nestle Ltd. p. 49-71.