Abstract
Background
Overweight and obese individuals have a reduced life expectancy due to cardiovascular disease (CVD), type 2 diabetes, stroke and cancer. Systemic inflammation and premature telomere shortening have been discussed as potential mechanisms linking these conditions. We investigated the relation of subcutaneous adipose tissue (SAT) distribution to leukocyte relative telomere length (RTL).
Methods
We measured RTL in 375 participants of the observational STYJOBS/EDECTA cohort (ClinicalTrials.gov Identifier NCT00482924) using a qPCR based method. SAT distribution was determined by lipometry yielding a percent body fat value and SAT thicknesses at 15 standardized locations across the entire body. A correlation analysis between RTL, age, sex, lipometry data and conventional body measures (body mass index [BMI], waist-, hip circumference, waist-to-hip ratio, waist-to-height ratio) was calculated. The strongest determinants of RTL were determined by a stepwise multiple regression analysis.
Results
RTL was not associated with age or sex. RTL was significantly negatively correlated with BMI, percent body fat, waist-, hip circumference and waist-to-height ratio. Furthermore, RTL correlated with SAT at the following locations: neck, triceps, biceps, upper back, front chest, lateral chest, upper abdomen, lower abdomen, lower back, hip, front thigh, lateral thigh, rear thigh and calf. Stepwise regression analysis revealed nuchal and hip SAT as the strongest predictors of RTL. No significant association was seen between RTL and waist-to-hip ratio.
Conclusions
RTL is negatively associated with parameters describing body fat composure. Nuchal and hip SAT thicknesses are the strongest predictors of RTL. Central obesity appears to correlate with premature genomic aging.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Maffetone PB, Rivera-Dominguez I, Laursen PB. Overfat and underfat: new terms and definitions long overdue. Front Pub Health 2016;4:279.10.3389/fpubh.2016.00279Search in Google Scholar PubMed PubMed Central
2. Tafeit E, Horejsi R, Pieber TR, Roller RE, Schnedl WJ, Wallner SJ, et al. Subcutaneous fat patterns in type-2 diabetic men and healthy controls. Coll Antropol 2008;32:607–14.Search in Google Scholar
3. Mangge H, Almer G, Truschnig-Wilders M, Schmidt A, Gasser R, Fuchs D. Inflammation, adiponectin, obesity and cardiovascular risk. Curr Med Chem 2010;17:4511–20.10.2174/092986710794183006Search in Google Scholar PubMed
4. Bluher M. Fat tissue and long life. Obes Facts 2008;1:176–82.10.1159/000145930Search in Google Scholar PubMed PubMed Central
5. Stohr BA, Xu L, Blackburn EH. The terminal telomeric DNA sequence determines the mechanism of dysfunctional telomere fusion. Mol Cell 2010;39:307–14.10.1016/j.molcel.2010.06.020Search in Google Scholar PubMed PubMed Central
6. Lakowa N, Trieu N, Flehmig G, Lohmann T, Schon MR, Dietrich A, et al. Telomere length differences between subcutaneous and visceral adipose tissue in humans. Biochem Biophys Res Commun 2015;457:426–32.10.1016/j.bbrc.2014.12.122Search in Google Scholar PubMed
7. Park Y, Peterson LL, Colditz GA. The plausibility of obesity paradox in cancer-point. Cancer Res 2018;78:1898–903.10.1158/0008-5472.CAN-17-3043Search in Google Scholar PubMed PubMed Central
8. Hall ME. Body mass index and heart failure mortality: more is less? JACC Heart Fail 2018;6:243–5.10.1016/j.jchf.2017.12.013Search in Google Scholar PubMed PubMed Central
9. Abramowitz MK, Hall CB, Amodu A, Sharma D, Androga L, Hawkins M. Muscle mass, BMI, and mortality among adults in the United States: a population-based cohort study. PLoS One 2018;13:e0194697.10.1371/journal.pone.0194697Search in Google Scholar PubMed PubMed Central
10. Revesz D, Milaneschi Y, Verhoeven JE, Lin J, Penninx BW. Longitudinal associations between metabolic syndrome components and telomere shortening. J Clin Endocrinol Metab 2015;100:3050–9.10.1210/JC.2015-1995Search in Google Scholar PubMed
11. Wulaningsih W, Kuh D, Wong A, Hardy R. Adiposity, telomere length, and telomere attrition in midlife: the 1946 British birth cohort. J Gerontol A Biol Sci Med Sci 2018;73:966–72.10.1093/gerona/glx151Search in Google Scholar PubMed PubMed Central
12. Yang M, Jiang P, Jin C, Wang J. Longer telomere length and its association with lower levels of C-peptide. Front Endocrinol (Lausanne) 2017;8:244.10.3389/fendo.2017.00244Search in Google Scholar PubMed PubMed Central
13. Batsis JA, Mackenzie TA, Vasquez E, Germain CM, Emeny RT,Rippberger P, et al. Association of adiposity, telomere length and mortality: data from the NHANES 1999–2002. Int J Obes (Lond) 2018;42:198–204.10.1038/ijo.2017.202Search in Google Scholar PubMed PubMed Central
14. Dershem R, Chu X, Wood GC, Benotti P, Still CD, Rolston DD. Changes in telomere length 3–5 years after gastric bypass surgery. Int J Obes (Lond) 2017;41:1718–20.10.1038/ijo.2017.156Search in Google Scholar PubMed PubMed Central
15. Iglesias Molli AE, Panero J, Dos Santos PC, Gonzalez CD, Vilarino J, Sereday M, et al. Metabolically healthy obese women have longer telomere length than obese women with metabolic syndrome. PLoS One 2017;12:e0174945.10.1371/journal.pone.0174945Search in Google Scholar PubMed PubMed Central
16. Guzzardi MA, Iozzo P, Salonen MK, Kajantie E, Eriksson JG. Maternal adiposity and infancy growth predict later telomere length: a longitudinal cohort study. Int J Obes (Lond) 2016;40:1063–9.10.1038/ijo.2016.58Search in Google Scholar PubMed
17. Muezzinler A, Mons U, Dieffenbach AK, Butterbach K, Saum KU, Schick M, et al. Body mass index and leukocyte telomere length dynamics among older adults: results from the ESTHER cohort. Exp Gerontol 2016;74:1–8.10.1016/j.exger.2015.11.019Search in Google Scholar PubMed
18. Mundstock E, Sarria EE, Zatti H, Mattos Louzada F, Kich Grun L, Herbert Jones M, et al. Effect of obesity on telomere length: systematic review and meta-analysis. Obesity 2015;23:2165–74.10.1002/oby.21183Search in Google Scholar PubMed
19. Muezzinler A, Zaineddin AK, Brenner H. Body mass index and leukocyte telomere length in adults: a systematic review and meta-analysis. Obes Rev 2014;15:192–201.10.1111/obr.12126Search in Google Scholar PubMed
20. Moller R, Tafeit E, Sudi K, Reibnegger G. Quantifying the ‘appleness’ or ‘pearness’ of the human body by subcutaneous adipose tissue distribution. Ann Hum Biol 2000;27:47–55.10.1080/030144600282370Search in Google Scholar PubMed
21. Moeller R, Horejsi R, Pilz S, Lang N, Sargsyan K, Dimitrova R, et al. Evaluation of risk profiles by subcutaneous adipose tissue topography in obese juveniles. Obesity 2007;15:1319–24.10.1038/oby.2007.154Search in Google Scholar PubMed
22. Moller R, Tafeit E, Pieber TR, Sudi K, Reibnegger G. Measurement of subcutaneous adipose tissue topography (SAT-Top) by means of a new optical device, LIPOMETER, and the evaluation of standard factor coefficients in healthy subjects. Am J Hum Biol 2000;12:231–9.10.1002/(SICI)1520-6300(200003/04)12:2<231::AID-AJHB9>3.0.CO;2-XSearch in Google Scholar
23. Cawthon RM. Telomere measurement by quantitative PCR. Nucl Acids Res 2002;30:e47.10.1093/nar/30.10.e47Search in Google Scholar
24. Tzanetakou IP, Katsilambros NL, Benetos A, Mikhailidis DP,Perrea DN. “Is obesity linked to aging?”: adipose tissue and the role of telomeres. Ageing Res Rev 2012;11:220–9.10.1016/j.arr.2011.12.003Search in Google Scholar
25. Dai Y, Wan X, Li X, Jin E, Li X. Neck circumference and future cardiovascular events in a high-risk population – a prospective cohort study. Lipids Health Dis 2016;15:46.10.1186/s12944-016-0218-3Search in Google Scholar
26. Koppad AK, Kaulgud RS, Arun BS. A study of correlation of neck circumference with Framingham risk score as a predictor of coronary artery disease. J Clin Diag Res 2017;11:OC17–20.10.7860/JCDR/2017/25710.10609Search in Google Scholar
27. Wulaningsih W, Watkins J, Matsuguchi T, Hardy R. Investigating the associations between adiposity, life course overweight trajectories, and telomere length. Aging 2016;8:2689–701.10.18632/aging.101036Search in Google Scholar
28. Chen S, Yeh F, Lin J, Matsuguchi T, Blackburn E, Lee ET, et al. Short leukocyte telomere length is associated with obesity in American Indians: the Strong Heart Family study. Aging (Albany, NY) 2014;6:380–9.10.18632/aging.100664Search in Google Scholar
29. Zgheib NK, Sleiman F, Nasreddine L, Nasrallah M, Nakhoul N, Isma’eel H, et al. Short telomere length is associated with aging, central obesity, poor sleep and hypertension in Lebanese individuals. Aging Dis 2018;9:77–89.10.14336/AD.2017.0310Search in Google Scholar
30. Weghuber D, Zelzer S, Stelzer I, Paulmichl K, Kammerhofer D, Schnedl W, et al. High risk vs. “metabolically healthy” phenotype in juvenile obesity – neck subcutaneous adipose tissue and serum uric acid are clinically relevant. Exp Clin Endocrinol Diabet 2013;121:384–90.10.1055/s-0033-1341440Search in Google Scholar
31. Mangge H, Zelzer S, Puerstner P, Schnedl WJ, Reeves G, Postolache TT, et al. Uric acid best predicts metabolically unhealthy obesity with increased cardiovascular risk in youth and adults. Obesity 2013;21:E71–7.10.1002/oby.20061Search in Google Scholar
32. Wallner-Liebmann SJ, Moeller R, Horejsi R, Jurimae T, Jurimae J, Maestu J, et al. Normal weight estonian prepubertal boys show a more cardiovascular-risk-associated adipose tissue distribution than austrian counterparts. ISRN Obes 2013;2013:506751.10.1155/2013/506751Search in Google Scholar PubMed PubMed Central
33. Kadakia MB, Fox CS, Scirica BM, Murphy SA, Bonaca MP, Morrow DA. Central obesity and cardiovascular outcomes in patients with acute coronary syndrome: observations from the MERLIN-TIMI 36 trial. Heart 2011;97:1782–7.10.1136/heartjnl-2011-300231Search in Google Scholar PubMed PubMed Central
34. Chen WZ, Chen XD, Ma LL, Zhang FM, Lin J, Zhuang CL, et al. Impact of visceral obesity and sarcopenia on short-term outcomes after colorectal cancer surgery. Dig Dis Sci 2018;63:1620–30.10.1007/s10620-018-5019-2Search in Google Scholar PubMed
35. Doyle SL, Mongan AM, Donohoe CL, Pidgeon GP, Sherlock M, Reynolds JV, et al. Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma. Dis Esophagus 2017;30:1–11.10.1093/dote/dox008Search in Google Scholar PubMed
36. Kuritzkes BA, Pappou EP, Kiran RP, Baser O, Fan L, Guo X, et al. Visceral fat area, not body mass index, predicts postoperative 30-day morbidity in patients undergoing colon resection for cancer. Int J Colorectal Dis 2018;8:1019–28.10.1007/s00384-018-3038-2Search in Google Scholar PubMed PubMed Central
37. Mangge H, Almer G, Haj-Yahya S, Grandits N, Gasser R, Pilz S, et al. Nuchal thickness of subcutaneous adipose tissue is tightly associated with an increased LMW/total adiponectin ratio in obese juveniles. Atherosclerosis 2009;203:277–83.10.1016/j.atherosclerosis.2008.06.013Search in Google Scholar PubMed
38. Mangge H, Becker K, Fuchs D, Gostner JM. Antioxidants, inflammation and cardiovascular disease. World J Cardiol 2014;6:462–77.10.4330/wjc.v6.i6.462Search in Google Scholar PubMed PubMed Central
39. Mangge H, Schauenstein K, Stroedter L, Griesl A, Maerz W, Borkenstein M. Low grade inflammation in juvenile obesity and type 1 diabetes associated with early signs of atherosclerosis. Exp Clin Endocrinol Diabetes 2004;112:378–82.10.1055/s-2004-821023Search in Google Scholar PubMed
40. Mangge H, Ciardi C, Becker K, Strasser B, Fuchs D, Gostner JM. Influence of antioxidants on leptin metabolism and its role in the pathogenesis of obesity. Adv Exp Med Biol 2017;960:399–413.10.1007/978-3-319-48382-5_17Search in Google Scholar PubMed
41. Wafa SW, Hamzaid H, Talib RA, Reilly JJ. Objectively measured habitual physical activity and sedentary behaviour in obese and non-obese Malaysian children. J Trop Pediatr 2014;60:161–3.10.1093/tropej/fmt093Search in Google Scholar PubMed
42. Werner C, Hanhoun M, Widmann T, Kazakov A, Semenov A, Poss J, et al. Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosis. J Am Coll Cardiol 2008;52:470–82.10.1016/j.jacc.2008.04.034Search in Google Scholar
43. Ludlow AT, Gratidao L, Ludlow LW, Spangenburg EE, Roth SM. Acute exercise activates p38 MAPK and increases the expression of telomere-protective genes in cardiac muscle. Exp Physiol 2017;102:397–410.10.1113/EP086189Search in Google Scholar
44. Martinez P, Gomez-Lopez G, Garcia F, Mercken E, Mitchell S, Flores JM, et al. RAP1 protects from obesity through its extratelomeric role regulating gene expression. Cell Rep 2013;3:2059–74.10.1016/j.celrep.2013.05.030Search in Google Scholar
45. Yeung F, Ramirez CM, Mateos-Gomez PA, Pinzaru A, Ceccarini G, Kabir S, et al. Nontelomeric role for Rap1 in regulating metabolism and protecting against obesity. Cell Rep 2013;3:1847–56.10.1016/j.celrep.2013.05.032Search in Google Scholar
46. Carulli L, Anzivino C, Baldelli E, Zenobii MF, Rocchi MB, Bertolotti M. Telomere length elongation after weight loss intervention in obese adults. Mol Genet Metab 2016;118:138–42.10.1016/j.ymgme.2016.04.003Search in Google Scholar
47. Laimer M, Melmer A, Lamina C, Raschenberger J, Adamovski P, Engl J, et al. Telomere length increase after weight loss induced by bariatric surgery: results from a 10 year prospective study. Int J Obes (Lond) 2016;40:773–8.10.1038/ijo.2015.238Search in Google Scholar
48. Tafeit E, Moller R, Sudi K, Horejsi R, Berg A, Reibnegger G. Orthogonal factor coefficient development of subcutaneous adipose tissue topography (SAT-Top) in girls and boys. Am J Phys Anthropol 2001;115:57–61.10.1002/ajpa.1056Search in Google Scholar
49. Moller R, Tafeit E, Smolle KH, Pieber TR, Ipsiroglu O, Duesse M, et al. Estimating percentage total body fat and determining subcutaneous adipose tissue distribution with a new noninvasive optical device LIPOMETER. Am J Hum Biol 2000;12:221–30.10.1002/(SICI)1520-6300(200003/04)12:2<221::AID-AJHB8>3.0.CO;2-2Search in Google Scholar
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