Circulating leptin levels are associated with adiposity in survivors of childhood brain tumors.
Adiposity
/ genetics
Adolescent
Biomarkers
/ blood
Brain Neoplasms
Cancer Survivors
Cardiovascular Diseases
/ diagnosis
Child
Cross-Sectional Studies
Diabetes Mellitus, Type 2
/ diagnosis
Early Diagnosis
Female
Humans
Leptin
/ blood
Male
Predictive Value of Tests
Risk Factors
Waist-Height Ratio
Waist-Hip Ratio
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 03 2020
13 03 2020
Historique:
received:
22
07
2019
accepted:
28
02
2020
entrez:
15
3
2020
pubmed:
15
3
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Survivors of Childhood Brain Tumors (SCBT) are at a higher risk of developing cardiovascular disease and type 2 diabetes compared to the general population. Adiposity is an important risk factor for the development of these outcomes, and identifying biomarkers of adiposity may help the stratification of survivors based on their cardiovascular risk or allow for early screening and interventions to improve cardiometabolic outcomes. Leptin is an adipokine that positively correlates with the adipose mass in the general population and is a predictor of adverse cardiometabolic outcomes, yet its association with adiposity in SCBT has not been studied. The aim of this study was to determine if leptin levels are associated with the adipose mass in SCBT, and to define its predictors. This cross-sectional study included 74 SCBT (n = 32 females) with 126 non-cancer controls (n = 59 females). Total adiposity was measured using Bioelectrical Impendence Analysis (BIA) and central adiposity was measured using waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). We used multivariable linear regression analysis to determine if leptin predicts adiposity in SCBT and adjusted for age, sex, puberty, and cancer status. Leptin correlated strongly with total (p < 0.001) and central (WHR p = 0.001; WHtR p < 0.001) adiposity in SCBT and non-cancer controls. In conclusion, leptin is a potential biomarker for adiposity in SCBT, and further investigation is needed to clarify if leptin is a predictor of future cardiometabolic risk in SCBT.
Identifiants
pubmed: 32170116
doi: 10.1038/s41598-020-61520-2
pii: 10.1038/s41598-020-61520-2
pmc: PMC7070034
doi:
Substances chimiques
Biomarkers
0
Leptin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4711Subventions
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : NA
Pays : International
Organisme : Regional Medical Associates of Hamilton
ID : NA
Pays : International
Références
McAloon, C. J. et al. The changing face of cardiovascular disease 2000–2012: An analysis of the world health organisation global health estimates data. International journal of cardiology 224, 256–264 (2016).
pubmed: 27664572
doi: 10.1016/j.ijcard.2016.09.026
Heron, M. P. Deaths: Leading causes for 2015 (2017).
Bhatnagar, P., Wickramasinghe, K., Williams, J., Rayner, M. & Townsend, N. The epidemiology of cardiovascular disease in the UK 2014. Heart 101, 1182–1189 (2015).
pubmed: 26041770
pmcid: 4515998
doi: 10.1136/heartjnl-2015-307516
Townsend, N. et al. Cardiovascular disease in Europe: epidemiological update 2016. European heart journal 37, 3232–3245 (2016).
pubmed: 27523477
doi: 10.1093/eurheartj/ehw334
Green, D. M., Hyland, A., Chung, C. S., Zevon, M. A. & Hall, B. C. Cancer and cardiac mortality among 15-year survivors of cancer diagnosed during childhood or adolescence. Journal of Clinical Oncology 17, 3207–3215 (1999).
pubmed: 10506620
doi: 10.1200/JCO.1999.17.10.3207
Heikens, J. et al. Long term survivors of childhood brain cancer have an increased risk for cardiovascular disease. Cancer 88, 2116–2121 (2000).
pubmed: 10813724
doi: 10.1002/(SICI)1097-0142(20000501)88:9<2116::AID-CNCR18>3.0.CO;2-U
Mulrooney, D. A. et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. Bmj 339, b4606 (2009).
pubmed: 19996459
pmcid: 3266843
doi: 10.1136/bmj.b4606
Armstrong, G. T. et al. Late mortality among 5-year survivors of childhood cancer: a summary from the Childhood Cancer Survivor Study. J Clin Oncol 27, 2328–2338 (2009).
pubmed: 19332714
pmcid: 2677921
doi: 10.1200/JCO.2008.21.1425
Meacham, L. R. et al. Diabetes mellitus in long-term survivors of childhood cancer: increased risk associated with radiation therapy: a report for the childhood cancer survivor study. Archives of internal medicine 169, 1381–1388 (2009).
pubmed: 19667301
pmcid: 3529471
doi: 10.1001/archinternmed.2009.209
Gurney, J. G. et al. Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors. Cancer 97, 663–673 (2003).
pubmed: 12548609
doi: 10.1002/cncr.11095
Bowers, D. C. et al. Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. Journal of Clinical Oncology 24, 5277–5282 (2006).
pubmed: 17088567
doi: 10.1200/JCO.2006.07.2884
Fall, T. et al. Age-and sex-specific causal effects of adiposity on cardiovascular risk factors. Diabetes 64, 1841–1852 (2015).
pubmed: 25712996
pmcid: 4407863
doi: 10.2337/db14-0988
Rana, J. S., Li, T. Y., Manson, J. E. & Hu, F. B. Adiposity compared with physical inactivity and risk of type 2 diabetes in women. Diabetes care 30, 53–58 (2007).
pubmed: 17192333
doi: 10.2337/dc06-1456
Wang, K. W. et al. Overweight, obesity and adiposity in survivors of childhood brain tumours: a systematic review and meta-analysis. Clinical Obesity (2017).
Wang, K. W. et al. Adiposity in childhood brain tumors: A report from the Canadian Study of Determinants of Endometabolic Health in Children (CanDECIDE Study). Scientific reports 7, 45078 (2017).
pubmed: 28327649
pmcid: 5361156
doi: 10.1038/srep45078
Siviero-Miachon, A. A., Spinola-Castro, A. M. & Guerra-Junior, G. Adiposity in childhood cancer survivors: insights into obesity physiopathology. Arquivos Brasileiros de Endocrinologia & Metabologia 53, 190–200 (2009).
doi: 10.1590/S0004-27302009000200011
Steinberger, J. et al. Cardiovascular risk and insulin resistance in childhood cancer survivors. The Journal of pediatrics 160, 494–499 (2012).
pubmed: 21920542
doi: 10.1016/j.jpeds.2011.08.018
Meacham, L. R. et al. Body mass index in long-term adult survivors of childhood cancer: A report of the Childhood Cancer Survivor Study. Cancer: Interdisciplinary International Journal of the American Cancer Society 103, 1730–1739 (2005).
doi: 10.1002/cncr.20960
Juonala, M. et al. Childhood adiposity, adult adiposity, and cardiovascular risk factors. New England Journal of Medicine 365, 1876–1885 (2011).
pubmed: 22087679
doi: 10.1056/NEJMoa1010112
Reilly, J. J. & Kelly, J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. International journal of obesity 35, 891 (2011).
pubmed: 20975725
doi: 10.1038/ijo.2010.222
Baker, J. L., Olsen, L. W. & Sørensen, T. I. A. Childhood body-mass index and the risk of coronary heart disease in adulthood. New England journal of medicine 357, 2329–2337 (2007).
pubmed: 18057335
doi: 10.1056/NEJMoa072515
Whitaker, R. C., Wright, J. A., Pepe, M. S., Seidel, K. D. & Dietz, W. H. Predicting obesity in young adulthood from childhood and parental obesity. New England Journal of Medicine 337, 869–873 (1997).
pubmed: 9302300
doi: 10.1056/NEJM199709253371301
Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425 (1994).
pubmed: 7984236
doi: 10.1038/372425a0
Schwartz, M. W., Peskind, E., Raskind, M., Boyko, E. J. & Porte, D. Jr Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nature medicine 2, 589 (1996).
pubmed: 8616722
doi: 10.1038/nm0596-589
Zimmet, P. et al. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study. Bmj 313, 965–969 (1996).
pubmed: 8892415
pmcid: 2352310
doi: 10.1136/bmj.313.7063.965
Ostlund, R. E. Jr, Yang, J. W., Klein, S. & Gingerich, R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. The journal of clinical endocrinology & metabolism 81, 3909–3913 (1996).
McNeely, M. J. et al. Association between baseline plasma leptin levels and subsequent development of diabetes in Japanese Americans. Diabetes Care 22, 65–70 (1999).
pubmed: 10333905
doi: 10.2337/diacare.22.1.65
Schmidt, M. I. et al. Leptin and incident type 2 diabetes: risk or protection? Diabetologia 49, 2086–2096 (2006).
pubmed: 16850292
doi: 10.1007/s00125-006-0351-z
Franks, P. W. et al. Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity. Obesity 13, 1476–1484 (2005).
doi: 10.1038/oby.2005.178
Wallace, A. M. et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation 104, 3052–3056 (2001).
pubmed: 11748099
doi: 10.1161/hc5001.101061
Galletti, F. et al. High-circulating leptin levels are associated with greater risk of hypertension in men independently of body mass and insulin resistance: results of an eight-year follow-up study. The Journal of Clinical Endocrinology & Metabolism 93, 3922–3926 (2008).
doi: 10.1210/jc.2008-1280
Shalitin, S. et al. Endocrine outcome in long-term survivors of childhood brain tumors. Hormone research in paediatrics 76, 113–122 (2011).
pubmed: 21691048
doi: 10.1159/000327584
Merchant, T. E. et al. Preirradiation endocrinopathies in pediatric brain tumor patients determined by dynamic tests of endocrine function. International Journal of Radiation Oncology* Biology* Physics 54, 45–50 (2002).
doi: 10.1016/S0360-3016(02)02888-2
Ward, E., DeSantis, C., Robbins, A., Kohler, B. & Jemal, A. Childhood and adolescent cancer statistics, 2014. CA: a cancer journal for clinicians 64, 83–103 (2014).
Chambless, L. B., Parker, S. L., Hassam-Malani, L., McGirt, M. J. & Thompson, R. C. Type 2 diabetes mellitus and obesity are independent risk factors for poor outcome in patients with high-grade glioma. Journal of neuro-oncology 106, 383–389 (2012).
pubmed: 21833800
doi: 10.1007/s11060-011-0676-4
Mertens, A. C. et al. Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. Journal of Clinical Oncology 19, 3163–3172 (2001).
pubmed: 11432882
doi: 10.1200/JCO.2001.19.13.3163
Prasad, P. K., Signorello, L. B., Friedman, D. L., Boice, J. D. & Pukkala, E. Long-term non-cancer mortality in pediatric and young adult cancer survivors in Finland. Pediatric blood & cancer 58, 421–427 (2012).
doi: 10.1002/pbc.23296
Lustig, R. H. et al. Risk Factors for the Development of Obesity in Children Surviving Brain Tumors. J Clin Endocrinol Metab 88, 611–616 (2003).
pubmed: 12574189
doi: 10.1210/jc.2002-021180
pmcid: 12574189
Pui, C. H. et al. Treatment outcomes in black and white children with cancer: results from the SEER database and St Jude Children’s Research Hospital, 1992 through 2007. J Clin Oncol 30, 2005–2012 (2012).
pubmed: 22547602
pmcid: 3383176
doi: 10.1200/JCO.2011.40.8617
Samaan, M. C. & Akhtar-Danesh, N. The impact of age and race on longevity in pediatric astrocytic tumors: A population-based study. Pediatric blood & cancer (2015).
Roth, C., Wilken, B., Hanefeld, F., Schroter, W. & Leonhardt, U. Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite. 138, 89 (1998).
Shaikh, M. G., Grundy, R. G. & Kirk, J. M. W. Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children. European journal of endocrinology 159, 791–797 (2008).
pubmed: 18819946
doi: 10.1530/EJE-08-0533
Green, E. D. et al. The human obese (OB) gene: RNA expression pattern and mapping on the physical, cytogenetic, and genetic maps of chromosome 7. Genome Research 5, 5–12 (1995).
pubmed: 8717050
doi: 10.1101/gr.5.1.5
Tartaglia, L. A. et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 83, 1263–1271 (1995).
pubmed: 8548812
doi: 10.1016/0092-8674(95)90151-5
Bingham, N. C., Anderson, K. K., Reuter, A. L., Stallings, N. R. & Parker, K. L. Selective loss of leptin receptors in the ventromedial hypothalamic nucleus results in increased adiposity and a metabolic syndrome. Endocrinology 149, 2138–2148 (2008).
pubmed: 18258679
pmcid: 2329259
doi: 10.1210/en.2007-1200
Couce, M. E., Burguera, B., Parisi, J. E., Jensen, M. D. & Lloyd, R. V. Localization of leptin receptor in the human brain. Neuroendocrinology 66, 145–150 (1997).
pubmed: 9380271
doi: 10.1159/000127232
Friedman, J. M. & Halaas, J. L. Leptin and the regulation of body weight in mammals. Nature 395, 763 (1998).
pubmed: 9796811
doi: 10.1038/27376
Arslan, N., Erdur, B. & Aydin, A. Hormones and cytokines in childhood obesity. Indian pediatrics 47, 829–839 (2010).
pubmed: 21048235
doi: 10.1007/s13312-010-0142-y
Pelleymounter, M. A. et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540–543 (1995).
doi: 10.1126/science.7624776
Tuominen, J. A. et al. Serum leptin concentration and fuel homeostasis in healthy man. European journal of clinical investigation 27, 206–211 (1997).
pubmed: 9088856
doi: 10.1046/j.1365-2362.1997.940642.x
Weigle, D. S. et al. Recombinant ob protein reduces feeding and body weight in the ob/ob mouse. The Journal of clinical investigation 96, 2065–2070 (1995).
pubmed: 7560100
pmcid: 185845
doi: 10.1172/JCI118254
Yannakoulia, M. et al. Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. The Journal of Clinical Endocrinology & Metabolism 88, 1730–1736 (2003).
doi: 10.1210/jc.2002-021604
Eriksson, J. et al. Leptin concentrations and their relation to body fat distribution and weight loss-A prospective study in individuals with impaired glucose tolerance. Hormone and metabolic research 31, 616–619 (1999).
pubmed: 10598830
doi: 10.1055/s-2007-978807
Thong, F. S., Hudson, R., Ross, R., Janssen, I. & Graham, T. E. Plasma leptin in moderately obese men: independent effects of weight loss and aerobic exercise. American Journal of Physiology-Endocrinology and Metabolism 279, E307–E313 (2000).
pubmed: 10913030
doi: 10.1152/ajpendo.2000.279.2.E307
Kimura, Y. et al. Association of adulthood weight gain with circulating adipokine and insulin resistance in the Japanese population. European journal of clinical nutrition 69, 462 (2015).
pubmed: 25469462
doi: 10.1038/ejcn.2014.257
Havel, P. J. et al. Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: effects of dietary fat content and sustained weight loss. The Journal of Clinical Endocrinology & Metabolism 81, 4406–4413 (1996).
Valle, M. et al. Relationship between high plasma leptin concentrations and metabolic syndrome in obese pre-pubertal children. International journal of obesity 27, 13 (2003).
pubmed: 12532148
doi: 10.1038/sj.ijo.0802154
Wabitsch, M. et al. Contribution of androgens to the gender difference in leptin production in obese children and adolescents. The Journal of clinical investigation 100, 808–813 (1997).
pubmed: 9259579
pmcid: 508252
doi: 10.1172/JCI119595
Saad, M. F. et al. Sexual dimorphism in plasma leptin concentration. The Journal of Clinical Endocrinology & Metabolism 82, 579–584 (1997).
Montague, C. T. et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387, 903 (1997).
pubmed: 9202122
doi: 10.1038/43185
Farooqi, I. S. et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. The Journal of clinical investigation 110, 1093–1103 (2002).
pubmed: 12393845
pmcid: 150795
doi: 10.1172/JCI0215693
Zhang, Y. & Scarpace, P. J. The role of leptin in leptin resistance and obesity. Physiology & behavior 88, 249–256 (2006).
doi: 10.1016/j.physbeh.2006.05.038
Martin, S. S., Qasim, A. & Reilly, M. P. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. Journal of the American College of Cardiology 52, 1201–1210 (2008).
pubmed: 18926322
pmcid: 4556270
doi: 10.1016/j.jacc.2008.05.060
Scarpace, P. J., Matheny, M., Tümer, N., Cheng, K. Y. & Zhang, Y. Leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats. Diabetologia 48, 1075–1083 (2005).
pubmed: 15864530
doi: 10.1007/s00125-005-1763-x
Lin, S., Thomas, T. C., Storlien, L. H. & Huang, X. F. Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice. International journal of obesity 24, 639 (2000).
pubmed: 10849588
doi: 10.1038/sj.ijo.0801209
Clemmensen, C. et al. Gut-brain cross-talk in metabolic control. Cell 168, 758–774 (2017).
pubmed: 28235194
pmcid: 5839146
doi: 10.1016/j.cell.2017.01.025
Heymsfield, S. B. et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. Jama 282, 1568–1575 (1999).
pubmed: 10546697
doi: 10.1001/jama.282.16.1568
Zelissen, P. M. J. et al. Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial. Diabetes, Obesity and Metabolism 7, 755–761 (2005).
pubmed: 16219020
doi: 10.1111/j.1463-1326.2005.00468.x
Considine, R. V. et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New England Journal of Medicine 334, 292–295 (1996).
pubmed: 8532024
doi: 10.1056/NEJM199602013340503
Trevaskis, J. L. et al. Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanisms. Endocrinology 149, 5679–5687 (2008).
pubmed: 18669592
doi: 10.1210/en.2008-0770
Trevaskis, J. L., Parkes, D. G. & Roth, J. D. Insights into amylin–leptin synergy. Trends in Endocrinology & Metabolism 21, 473–479 (2010).
doi: 10.1016/j.tem.2010.03.006
Müller, T. D. et al. Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21. Journal of Peptide Science 18, 383–393 (2012).
pubmed: 22565812
doi: 10.1002/psc.2408
Chen, K. Y. et al. RM-493, a melanocortin-4 receptor (MC4R) agonist, increases resting energy expenditure in obese individuals. The. Journal of Clinical Endocrinology & Metabolism 100, 1639–1645 (2015).
doi: 10.1210/jc.2014-4024
Unniappan, S. & Kieffer, T. J. Leptin extends the anorectic effects of chronic PYY (3-36) administration in ad libitum-fed rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 295, R51–R58 (2008).
pubmed: 18417649
pmcid: 2494814
doi: 10.1152/ajpregu.00234.2007
Wang, L., Barachina, M. D., Martınez, V., Wei, J. Y. & Tache, Y. Synergistic interaction between CCK and leptin to regulate food intake. Regulatory peptides 92, 79–85 (2000).
pubmed: 11024569
doi: 10.1016/S0167-0115(00)00153-1
Samaan, M. C., Thabane, L., Burrow, S., Dillenburg, R. F. & Scheinemann, K. Canadian Study of Determinants of Endometabolic Health in ChIlDrEn (CanDECIDE study): a cohort study protocol examining the mechanisms of obesity in survivors of childhood brain tumours. BMJ open 3, e002869 (2013).
pubmed: 23794554
pmcid: 3686178
doi: 10.1136/bmjopen-2013-002869
Samaan, M. C. et al. Recruitment feasibility to a cohort study of endocrine and metabolic health among survivors of childhood brain tumours: a report from the Canadian study of Determinants of Endometabolic Health in ChIlDrEn (CanDECIDE). BMJ Open 4, e005295 (2014).
pubmed: 24969784
pmcid: 4078774
doi: 10.1136/bmjopen-2014-005295
Nihiser, A. J. et al. Body mass index measurement in schools. J Sch Health 77, 651–671; quiz 722–654 (2007).
pubmed: 18076411
doi: 10.1111/j.1746-1561.2007.00249.x
Kuczmarski, R. J. et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11, 1–190 (2002).
Released, S. I. PASW Statistics for Windows, Version 24. (2016).
Ghasemi, A. & Zahediasl, S. Normality tests for statistical analysis: a guide for non-statisticians. International journal of endocrinology and metabolism 10, 486 (2012).
pubmed: 23843808
pmcid: 3693611
doi: 10.5812/ijem.3505