Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Adipocyte and Cell Biology

Adipocyte size, adipose tissue fibrosis, macrophage infiltration and disease risk are different in younger and older individuals with childhood versus adulthood onset obesity

Subjects

Abstract

Background

The timing of obesity onset and age have been shown to affect the risk of obesity-related comorbidities, although the impact of each of these factors on markers of adipose tissue function remains unclear.

Objective

The aim of this study was to determine whether differences in regional adipose tissue characteristics vary with age and age of obesity onset, and whether these differences are associated with the markers of cardiometabolic health.

Methods

Adipose tissue samples were obtained from 80 female bariatric surgery candidates who were classified by age of obesity onset and age into 4 groups: (1) younger adults (<40 y) with childhood-onset obesity (<18 y) (Child-Young); (2) younger adults with adulthood-onset obesity (>18 y) (Adult-Young); (3) older adults (>55 y) with childhood-onset obesity (Child-Old); and (4) older adults with adulthood-onset obesity (Adult-Old). Adipocyte diameter, adipose tissue fibrosis, and macrophage infiltration were determined in subcutaneous (SAT) and visceral adipose tissue (VAT). Clinical parameters were obtained from participants’ medical records.

Results

Visceral adipocyte size in the Child-Young group was the smallest of all the groups. Age affected visceral infiltration of M1-like cells with greater percent of M1-like cells in the Adult-Old and Child-Old groups. Though not significant, a stepwise increase in M2-like macrophages in VAT was observed with Adult-Young having the smallest followed by Adult-Old, Child-Young, and Child-Old having the greatest percent of M2-like macrophages. Pericellular fibrosis accumulation in SAT and VAT varied with both age and onset, particularly in the Child-Old group, which had the lowest fibrosis levels. Markers of cardiometabolic health (fasting glucose, glycated hemoglobin, total, HDL- and LDL-cholesterol and triglyceride concentrations) were positively and well-associated with adipose tissue characteristics of the Child-Old group but not of the Adult-Young group.

Conclusion

Older adults with childhood-onset obesity, who had the greatest duration of obesity exposure, were particularly vulnerable to the cardiometabolic effects associated with perturbations in adipose tissue characteristics. These results suggest that age and age of obesity onset may have independent and cumulative effects on obesity pathology.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Histologic measurements of adipocyte size.
Fig. 2: Immunohistochemical detection of macrophages.
Fig. 3: Histologic measurements of adipose tissue fibrosis.

Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Int J Obes. 2011;35:891–8.

    CAS  Google Scholar 

  2. Evensen E, Wilsgaard T, Furberg AS, Skeie G. Tracking of overweight and obesity from early childhood to adolescence in a population-based cohort—the Tromso Study, Fit Futures. BMC Pediatr. 2016;16:64.

    PubMed  PubMed Central  Google Scholar 

  3. Falkstedt D, Hemmingsson T, Rasmussen F, Lundberg I. Body mass index in late adolescence and its association with coronary heart disease and stroke in middle age among Swedish men. Int J Obes. 2007;31:777–83.

    CAS  Google Scholar 

  4. Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett PH, Looker HC. Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med. 2010;362:485–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Park MH, Sovio U, Viner RM, Hardy RJ, Kinra S. Overweight in childhood, adolescence and adulthood and cardiovascular risk in later life: pooled analysis of three british birth cohorts. PLoS ONE. 2013;8:e70684.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Brook CG, Lloyd JK, Wolf OH. Relation between age of onset of obesity and size and number of adipose cells. Br Med J. 1972;2:25–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Salans LB, Cushman SW, Weismann RE. Studies of human adipose tissue. Adipose cell size and number in nonobese and obese patients. J Clin Investig. 1973;52:929–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Sjostrom L, Bjorntorp P. Body composition and adipose cellularity in human obesity. Acta Med Scand. 1974;195:201–11.

    CAS  PubMed  Google Scholar 

  9. Tam BT, Murphy J, Khor N, Morais JA, Santosa S. Acetyl-CoA regulation, OXPHOS integrity and leptin levels are different in females with childhood vs adulthood onset of obesity. Endocrinology. 2020;161:1–15.

    CAS  Google Scholar 

  10. Houston DK, Nicklas BJ, Zizza CA. Weighty concerns: the growing prevalence of obesity among older adults. J Am Diet Assoc. 2009;109:1886–95.

    CAS  PubMed  Google Scholar 

  11. Samper-Ternent R, Al Snih S. Obesity in older adults: epidemiology and implications for disability and disease. Rev Clin Gerontol. 2012;22:10–34.

    PubMed  PubMed Central  Google Scholar 

  12. Tam BT, Morais JA, Santosa S. Obesity and ageing: two sides of the same coin. Obes Rev. 2020;21:e12991.

    PubMed  Google Scholar 

  13. Lee JJ, Pedley A, Hoffmann U, Massaro JM, Levy D, Long MT. Visceral and intrahepatic fat are associated with cardiometabolic risk factors above other ectopic fat depots: the Framingham Heart Study. Am J Med. 2018;131:684–92.e12.

    PubMed  PubMed Central  Google Scholar 

  14. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116:39–48.

    PubMed  Google Scholar 

  15. Hamdy O, Porramatikul S, Al-Ozairi E. Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr Diabetes Rev. 2006;2:367–73.

    PubMed  Google Scholar 

  16. Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev. 2010;11:11–8.

    PubMed  Google Scholar 

  17. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Investig. 2011;121:2094–101.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Laforest S, Labrecque J, Michaud A, Cianflone K, Tchernof A. Adipocyte size as a determinant of metabolic disease and adipose tissue dysfunction. Crit Rev Clin Lab Sci. 2015;52:301–13.

    CAS  PubMed  Google Scholar 

  19. Sun K, Tordjman J, Clement K, Scherer PE. Fibrosis and adipose tissue dysfunction. Cell Metab. 2013;18:470–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Datta R, Podolsky MJ, Atabai K. Fat fibrosis: friend or foe?. JCI Insight. 2018;3:e122289.

    PubMed Central  Google Scholar 

  21. Tchernof A, Despres JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013;93:359–404.

    CAS  PubMed  Google Scholar 

  22. Laforest S, Pelletier M, Michaud A, Daris M, Descamps J, Soulet D, et al. Histomorphometric analyses of human adipose tissues using intact, flash-frozen samples. Histochem Cell Biol. 2018;149:209–18.

    CAS  PubMed  Google Scholar 

  23. Michaud A, Laforest S, Pelletier M, Nadeau M, Simard S, Daris M, et al. Abdominal adipocyte populations in women with visceral obesity. Eur J Endocrinol. 2016;174:227–39.

    CAS  PubMed  Google Scholar 

  24. Vijay J, Gauthier MF, Biswell RL, Louiselle DA, Johnston JJ, Cheung WA, et al. Single-cell analysis of human adipose tissue identifies depot and disease specific cell types. Nat Metab. 2020;2:97–109.

    PubMed  Google Scholar 

  25. Michaud A, Tordjman J, Pelletier M, Liu Y, Laforest S, Noel S, et al. Relevance of omental pericellular adipose tissue collagen in the pathophysiology of human abdominal obesity and related cardiometabolic risk. Int J Obes. 2016;40:1823–31.

    CAS  Google Scholar 

  26. Henegar C, Tordjman J, Achard V, Lacasa D, Cremer I, Guerre-Millo M, et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol. 2008;9:R14.

    PubMed  PubMed Central  Google Scholar 

  27. Norris T, Cole TJ, Bann D, Hamer M, Hardy R, Li L, et al. Duration of obesity exposure between ages 10 and 40 years and its relationship with cardiometabolic disease risk factors: a cohort study. PLoS Med. 2020;17:e1003387.

    PubMed  PubMed Central  Google Scholar 

  28. Luo J, Hodge A, Hendryx M, Byles JE. Age of obesity onset, cumulative obesity exposure over early adulthood and risk of type 2 diabetes. Diabetologia. 2020;63:519–27.

    CAS  PubMed  Google Scholar 

  29. Bays HE. Adiposopathy is “sick fat” a cardiovascular disease? J Am Coll Cardiol. 2011;57:2461–73.

    CAS  PubMed  Google Scholar 

  30. Bjorntorp P, Bengtsson C, Blohme G, Jonsson A, Sjostrom L, Tibblin E, et al. Adipose tissue fat cell size and number in relation to metabolism in randomly selected middle-aged men and women. Metabolism. 1971;20:927–35.

    CAS  PubMed  Google Scholar 

  31. Bonzon-Kulichenko E, Molto E, Pintado C, Fernandez A, Arribas C, Schwudke D, et al. Changes in visceral adipose tissue plasma membrane lipid composition in old rats are associated with adipocyte hypertrophy with aging. J Gerontol A Biol Sci Med Sci. 2018;73:1139–46.

    CAS  PubMed  Google Scholar 

  32. Hemmeryckx B, Loeckx D, Dresselaers T, Himmelreich U, Hoylaerts MF, Lijnen HR. Age-associated adaptations in murine adipose tissues. Endocr J. 2010;57:925–30.

    PubMed  Google Scholar 

  33. Ktotkiewski M, Sjostrom L, Bjorntorp P, Smith U. Regional adipose tissue cellularity in relation to metabolism in young and middle-aged women. Metabolism. 1975;24:703–10.

    CAS  PubMed  Google Scholar 

  34. Lumeng CN, Liu J, Geletka L, Delaney C, Delproposto J, Desai A, et al. Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue. J Immunol. 2011;187:6208–16.

    CAS  PubMed  Google Scholar 

  35. Ledoux S, Coupaye M, Essig M, Msika S, Roy C, Queguiner I, et al. Traditional anthropometric parameters still predict metabolic disorders in women with severe obesity. Obesity. 2010;18:1026–32.

    PubMed  Google Scholar 

  36. O’Connell J, Lynch L, Cawood TJ, Kwasnik A, Nolan N, Geoghegan J, et al. The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity. PLoS ONE. 2010;5:e9997.

    PubMed  PubMed Central  Google Scholar 

  37. Veilleux A, Caron-Jobin M, Noel S, Laberge PY, Tchernof A. Visceral adipocyte hypertrophy is associated with dyslipidemia independent of body composition and fat distribution in women. Diabetes. 2011;60:1504–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Turner L, Santosa S. Putting ATM to BED: how adipose tissue macrophages are affected by bariatric surgery, exercise, and dietary fatty acids. Adv Nutr. 2021;12:1893–910.

    PubMed  PubMed Central  Google Scholar 

  39. Dam V, Sikder T, Santosa S. From neutrophils to macrophages: differences in regional adipose tissue depots. Obes Rev. 2016;17:1–17.

    CAS  PubMed  Google Scholar 

  40. Aron-Wisnewsky J, Tordjman J, Poitou C, Darakhshan F, Hugol D, Basdevant A, et al. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab. 2009;94:4619–23.

    CAS  PubMed  Google Scholar 

  41. Cancello R, Tordjman J, Poitou C, Guilhem G, Bouillot JL, Hugol D, et al. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes. 2006;55:1554–61.

    CAS  PubMed  Google Scholar 

  42. Harman-Boehm I, Bluher M, Redel H, Sion-Vardy N, Ovadia S, Avinoach E, et al. Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab. 2007;92:2240–7.

    CAS  PubMed  Google Scholar 

  43. Kralova Lesna I, Kralova A, Cejkova S, Fronek J, Petras M, Sekerkova A, et al. Characterisation and comparison of adipose tissue macrophages from human subcutaneous, visceral and perivascular adipose tissue. J Transl Med. 2016;14:208.

    PubMed  PubMed Central  Google Scholar 

  44. Nakajima S, Koh V, Kua LF, So J, Davide L, Lim KS, et al. Accumulation of CD11c+CD163+ adipose tissue macrophages through upregulation of intracellular 11beta-HSD1 in human obesity. J Immunol. 2016;197:3735–45.

    CAS  PubMed  Google Scholar 

  45. Verboven K, Wouters K, Gaens K, Hansen D, Bijnen M, Wetzels S, et al. Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans. Sci Rep. 2018;8:4677.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Jerschow EA S, Barzilai N, Rosenstreich D. Macrophages accumulation in visceral and subcutaneous adipose tissue correlates with age. J Allergy Clin Immunol. 2007;119:S179.

    Google Scholar 

  47. Einstein FH, Huffman DM, Fishman S, Jerschow E, Heo HJ, Atzmon G, et al. Aging per se increases the susceptibility to free fatty acid-induced insulin resistance. J Gerontol A Biol Sci Med Sci. 2010;65:800–8.

    PubMed  Google Scholar 

  48. Dankel SN, Svard J, Mattha S, Claussnitzer M, Kloting N, Glunk V, et al. COL6A3 expression in adipocytes associates with insulin resistance and depends on PPARgamma and adipocyte size. Obesity. 2014;22:1807–13.

    CAS  PubMed  Google Scholar 

  49. Guglielmi V, Cardellini M, Cinti F, Corgosinho F, Cardolini I, D’Adamo M, et al. Omental adipose tissue fibrosis and insulin resistance in severe obesity. Nutr Diabetes. 2015;5:e175.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Spencer M, Unal R, Zhu B, Rasouli N, McGehee RE Jr., Peterson CA, et al. Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance. J Clin Endocrinol Metab. 2011;96:E1990–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Spencer M, Yao-Borengasser A, Unal R, Rasouli N, Gurley CM, Zhu B, et al. Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation. Am J Physiol Endocrinol Metab. 2010;299:E1016–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A, et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes. 2010;59:2817–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Muir LA, Neeley CK, Meyer KA, Baker NA, Brosius AM, Washabaugh AR, et al. Adipose tissue fibrosis, hypertrophy, and hyperplasia: correlations with diabetes in human obesity. Obesity. 2016;24:597–605.

    CAS  PubMed  Google Scholar 

  54. McCulloch LJ, Rawling TJ, Sjoholm K, Franck N, Dankel SN, Price EJ, et al. COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity. Endocrinology. 2015;156:134–46.

    PubMed  Google Scholar 

  55. Vila IK, Badin PM, Marques MA, Monbrun L, Lefort C, Mir L, et al. Immune cell Toll-like receptor 4 mediates the development of obesity- and endotoxemia-associated adipose tissue fibrosis. Cell Rep. 2014;7:1116–29.

    CAS  PubMed  Google Scholar 

  56. Michaud A, Drolet R, Noel S, Paris G, Tchernof A. Visceral fat accumulation is an indicator of adipose tissue macrophage infiltration in women. Metabolism. 2012;61:689–98.

    CAS  PubMed  Google Scholar 

  57. Pasarica M, Gowronska-Kozak B, Burk D, Remedios I, Hymel D, Gimble J, et al. Adipose tissue collagen VI in obesity. J Clin Endocrinol Metab. 2009;94:5155–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Murphy J, Delaney KZ, Dam V, Tam BT, Khor N, Tsoukas MA, et al. Sex affects regional variations in subcutaneous adipose tissue T cells but not macrophages in adults with obesity. Obesity. 2020;28:2310–4.

    CAS  PubMed  Google Scholar 

  59. Dahl AK, Reynolds CA. Accuracy of recalled body weight—a study with 20-years of follow-up. Obesity. 2013;21:1293–8.

    PubMed  Google Scholar 

  60. Lin CJ, DeRoo LA, Jacobs SR, Sandler DP. Accuracy and reliability of self-reported weight and height in the Sister Study. Public Health Nutr. 2012;15:989–99.

    PubMed  Google Scholar 

Download references

Acknowledgements

Sylvia Santosa holds a Canada Research Chair-Tier 2 in Clinical Nutrition. Laurent Turner is supported by a PERFORM graduate student award. This research was made possible by in-kind equipment support from the PERFORM Center, and funding from a Natural Science and Engineering Research Council of Canada (NSERC) Discovery Grant. The authors thank Dr. Alisa Piekny for her help and guidance in the microscopy analyses, the participants who consented to be tissue donors, and acknowledge the invaluable collaboration of the surgery team, bariatric surgeons and biobank staff of the IUCPQ.

Author information

Authors and Affiliations

Authors

Contributions

LT was responsible for optimizing the research protocols, methodology, formal and statistical analysis, interpreting results, and writing of the manuscript. MFG was responsible for optimizing the research protocols and manuscript revision. AL was responsible for clinical aspects of patient participation and surgical sampling as well as manuscript revision. AT was responsible for the conceptualization of the study, methodology, funding, and manuscript revision. SS, as the principal investigator, was responsible for the conceptualization of the study, funding and manuscript revision.

Corresponding author

Correspondence to S. Santosa.

Ethics declarations

Competing interests

The authors have no competing interests to declare with regards to the content of this study. SS is a member of the Scientific Advisory Panel for Nutritional Fundamentals for Health Inc. AT receives research funding from Johnson & Johnson, Medtronic, and GI Windows for studies on bariatric surgery; and acted as a consultant for Bausch Health, Novo Nordisk, Eli Lilly, and Biotwin.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Turner, L., Gauthier, MF., Lafortune, A. et al. Adipocyte size, adipose tissue fibrosis, macrophage infiltration and disease risk are different in younger and older individuals with childhood versus adulthood onset obesity. Int J Obes 46, 1859–1866 (2022). https://doi.org/10.1038/s41366-022-01192-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-022-01192-2

Search

Quick links