Morphology and functional organization of subcutaneous adipose tissue: modern concepts of structural and functional heterogeneity and age-related changes (systematic literature review)
https://doi.org/10.20340/vmi-rvz.2025.3.MORPH.3
Abstract
Introduction. Subcutaneous adipose tissue represents a complex multi-component system playing a pivotal role in metabolic, immunological, and thermoregulatory processes. Contemporary understanding of structural and functional heterogeneity of adipose tissue has fundamentally changed our perception of its role in metabolic disease pathogenesis and aging processes.
Objective. To conduct a systematic analysis of current data on morphological organization of subcutaneous adipose tissue, its layered structure, and age-related changes with emphasis on clinical significance for aesthetic medicine.
Materials and methods. A systematic literature search was performed in PubMed, Scopus, Web of Science, and RSCI databases for the period 2015-2024. Keywords included: "subcutaneous adipose tissue", "dermal white adipose tissue", "superficial fascia", "aging", "morphology". Of 89 sources analyzed, 52 were included in the final analysis according to inclusion criteria.
Results. Subcutaneous adipose tissue is characterized by pronounced morphological heterogeneity and can be divided into dermal white adipose tissue (dWAT) and superficial white adipose tissue (sWAT). dWAT is localized in the lower dermis as discrete adipose clusters, while sWAT forms a continuous layer separated from dWAT by the superficial fascia. dWAT cells are characterized by smaller size (30-50 μm), high expression of UCP1 and PRDM16 markers, and active participation in wound healing and thermoregulation. sWAT contains large adipocytes (80-130 μm) organized into lobules separated by fibrous septa. Age-related changes include progressive reduction in dWAT volume (up to 40% by age 60), altered collagen I/III ratio, decreased vascularization and lymphatic drainage. Molecular aging mechanisms are associated with suppressed PPARγ and CEBPα expression and reduced Wnt/β-catenin signaling pathway activity.
Conclusion. Understanding the morphological heterogeneity of subcutaneous adipose tissue is critically important for developing personalized approaches in aesthetic medicine. Future research should focus on studying molecular mechanisms of different adipocyte population differentiation and developing targeted methods for age-related change correction.
Keywords
About the Authors
M. A. ShirshakovaRussian Federation
Mariya A. Shirshakova - Cand. Sci. (Med.), founder of the NBMC clinic and the Beauty Praktikum educational center.
Author's contribution: study concept and design, literature analysis, article writing.
7, Sadovaya-Kudrinskaya St., building 13, Moscow, 123242
Competing Interests:
The authors declare no competing interests. Supilnikov A.A. is a member of the editorial board of the journal, did not participate in the decision to publish the article.
S. E. Shemyakov
Russian Federation
Sergey E. Shemyakov - Dr. Sci. (Med.), Professor, Deputy Director, Yu.M. Lopukhin Institute of Anatomy and Morphology, Head of Department
Author's contribution: study methodology, literature analysis, article editing.
1, Ostrovityanova St., Moscow, 117997
Competing Interests:
The authors declare no competing interests. Supilnikov A.A. is a member of the editorial board of the journal, did not participate in the decision to publish the article.
A. A. Supil'nikov
Russian Federation
Aleksey A. Supilnikov - Cand. Sci. (Med.), Associate Professor, Deputy Director, Yu.M. Lopukhin Institute of Anatomy and Morphology. Lopukhina; First Vice-Rector for Research
Author's contribution: research methodology, literature analysis, article editing.
1, Ostrovityanova St., Moscow, 117997;
Chapaevskaya St., 227, Samara, 443001
Competing Interests:
The authors declare no competing interests. Supilnikov A.A. is a member of the editorial board of the journal, did not participate in the decision to publish the article.
Yu. E. Mel'nikova
Russian Federation
Yuliya E. Mel'nikova - Dermatovenerologist, cosmetologist at the NBMC clinic.
Author's contribution: literature search and analysis, data systematization, manuscript preparation.
7, Sadovaya-Kudrinskaya St., building 13, Moscow, 123242
Competing Interests:
The authors declare no competing interests. Supilnikov A.A. is a member of the editorial board of the journal, did not participate in the decision to publish the article.
References
1. Rydén M., Arner P. Subcutaneous adipocyte lipolysis contributes to circulating lipid levels // Arterioscler. Thromb. Vasc. Biol. 2017. Vol. 37, N 9. P. 1782-1787. DOI: 10.1161/ATVBAHA.117.309759
2. Kruglikov I.L., Scherer P.E. Dermal adipocytes: from irrelevance to metabolic targets? // Trends Endocrinol. Metab. 2016. Vol. 27, N 1. P. 1-10. DOI: 10.1016/j.tem.2015.11.002
3. Wojciechowicz K., Gledhill K., Ambler C.A., et al. Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4 // PLoS One. 2013. Vol. 8, N 3. P. e59811. DOI: 10.1371/journal.pone.0059811
4. Alexander C.M., Kasza I., Yen C.L., et al. Dermal white adipose tissue: a new component of the thermogenic response // J. Lipid Res. 2015. Vol. 56, N 11. P. 2061-2069. DOI: 10.1194/jlr.R062893
5. Driskell R.R., Jahoda C.A., Chuong C.M., et al. Defining dermal adipose tissue // Exp. Dermatol. 2014. Vol. 23, N 9. P. 629-631. DOI: 10.1111/exd.12450
6. Zhang Z., Deng Q., Zhang Y., et al. Subcutaneous adipose tissue: a favorable mechanical environment for nerve regeneration // Acta Biomater. 2021. Vol. 125. P. 253-265. DOI: 10.1016/j.actbio.2021.02.030
7. Bose S., Kryczek I., Kowalkowski M., et al. IFNγ regulation of epithelial-mesenchymal transition and cancer stem cells in adipose tissue inflammation // Cancer Res. 2020. Vol. 80, N 5. P. 1062-1074. DOI: 10.1158/0008-5472.CAN-19-2873
8. Palmer A.K., Tchkonia T., LeBrasseur N.K., et al. Cellular senescence in type 2 diabetes: a therapeutic opportunity // Diabetes. 2015. Vol. 64, N 7. P. 2289-2298. DOI: 10.2337/db14-1820
9. Stout M.B., Justice J.N., Nicklas B.J., Kirkland J.L. Physiological aging: links among adipose tissue dysfunction, diabetes, and frailty // Physiology (Bethesda). 2017. Vol. 32, N 1. P. 9-19. DOI: 10.1152/physiol.00012.2016
10. Rivera-Gonzalez G., Shook B., Horsley V. Adipocytes in skin health and disease // Cold Spring Harb. Perspect. Med. 2014. Vol. 4, N 3. P. a015271. DOI: 10.1101/cshperspect.a015271
11. Schmidt B.A., Horsley V. Intradermal adipocytes mediate fibroblast recruitment during skin wound healing // Development. 2013. Vol. 140, N 7. P. 1517-1527. DOI: 10.1242/dev.087593
12. Zhang L.J., Guerrero-Juarez C.F., Hata T., et al. Innate immunity. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection // Science. 2015. Vol. 347, N 6217. P. 67-71. DOI: 10.1126/science.1260972
13. Shook B.A., Wasko R.R., Rivera-Gonzalez G.C., et al. Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair // Science. 2018. Vol. 362, N 6417. P. eaar2971. DOI: 10.1126/science.aar2971
14. Festa E., Fretz J., Berry R., et al. Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling // Cell. 2011. Vol. 146, N 5. P. 761-771. DOI: 10.1016/j.cell.2011.07.019
15. Ghaben A.L., Scherer P.E. Adipogenesis and metabolic health // Nat. Rev. Mol. Cell Biol. 2019. Vol. 20, N 4. P. 242-258. DOI: 10.1038/s41580-018-0093-z
16. Jeffery E., Church C.D., Holtrup B., et al. Rapid depot-specific activation of adipocyte precursor cells at the onset of obesity // Nat. Cell Biol. 2015. Vol. 17, N 4. P. 376-385. DOI: 10.1038/ncb3122
17. McDonald M.E., Li C., Bian H., et al. Myofibroblasts derived from dermal white adipose tissue drive skin wound healing // Cell Stem Cell. 2022. Vol. 29, N 12. P. 1650-1665.e9. DOI: 10.1016/j.stem.2022.11.004
18. Kasza I., Suh J.M., Wollny D., et al. Syndecan-1 is required to maintain intradermal fat and prevent cold stress // PLoS Genet. 2014. Vol. 10, N 8. P. e1004514. DOI: 10.1371/journal.pgen.1004514
19. Marangoni R.G., Korman B.D., Wei J., et al. Myofibroblasts in murine cutaneous fibrosis originate from adiponectin-positive intradermal progenitors // Arthritis Rheumatol. 2015. Vol. 67, N 4. P. 1062-1073. DOI: 10.1002/art.38990
20. Plikus M.V., Guerrero-Juarez C.F., Ito M., et al. Regeneration of fat cells from myofibroblasts during wound healing // Science. 2017. Vol. 355, N 6326. P. 748-752. DOI: 10.1126/science.aai8792
21. Kershaw E.E., Flier J.S. Adipose tissue as an endocrine organ // J. Clin. Endocrinol. Metab. 2004. Vol. 89, N 6. P. 2548-2556. DOI: 10.1210/jc.2004-0395
22. Blüher M. Adipose tissue dysfunction contributes to obesity related metabolic diseases // Best Pract. Res. Clin. Endocrinol. Metab. 2013. Vol. 27, N 2. P. 163-177. DOI: 10.1016/j.beem.2013.02.005
23. Cao Y. Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity // Cell Metab. 2013. Vol. 18, N 4. P. 478-489. DOI: 10.1016/j.cmet.2013.08.008
24. Crewe C., An Y.A., Scherer P.E. The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis // J. Clin. Invest. 2017. Vol. 127, N 1. P. 74-82. DOI: 10.1172/JCI88883
25. Kuan E.L., Ivanov S., Bridenbaugh E.A., et al. Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells // J. Immunol. 2015. Vol. 194, N 11. P. 5200-5210. DOI: 10.4049/jimmunol.1500221
26. Sadick N.S., Dayan S., Kaufman J., et al. The facial adipose system: its role in facial aging and approaches to volume restoration // Dermatol. Surg. 2015. Vol. 41, Suppl 1. P. S333-339. DOI: 10.1097/DSS.0000000000000517
27. Coleman S.R., Grover R. The anatomy of the aging face: volume loss and changes in 3-dimensional topography // Aesthet. Surg. J. 2006. Vol. 26, N 1S. P. S4-9. DOI: 10.1016/j.asj.2005.09.012
28. Tchkonia T., Morbeck D.E., Von Zglinicki T., et al. Fat tissue, aging, and cellular senescence // Aging Cell. 2010. Vol. 9, N 5. P. 667-684. DOI: 10.1111/j.1474-9726.2010.00608.x
29. Xu M., Palmer A.K., Ding H., et al. Targeting senescent cells enhances adipogenesis and metabolic function in old age // Elife. 2015. Vol. 4. P. e12997. DOI: 10.7554/eLife.12997
30. Kuk J.L., Saunders T.J., Davidson L.E., Ross R. Age-related changes in total and regional fat distribution // Ageing Res. Rev. 2009. Vol. 8, N 4. P. 339-348. DOI: 10.1016/j.arr.2009.06.001
31. Pellegrinelli V., Carobbio S., Vidal-Puig A. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues // Diabetologia. 2016. Vol. 59, N 6. P. 1075-1088. DOI: 10.1007/s00125-016-3933-4
32. Palmer A.K., Kirkland J.L. Aging and adipose tissue: potential interventions for diabetes and regenerative medicine // Exp. Gerontol. 2016. Vol. 86. P. 97-105. DOI: 10.1016/j.exger.2016.02.013
33. Cartwright M.J., Tchkonia T., Kirkland J.L. Aging in adipocytes: potential impact of inherent, depot-specific mechanisms // Exp. Gerontol. 2007. Vol. 42, N 6. P. 463-471. DOI: 10.1016/j.exger.2007.03.003
34. Kruglikov I.L., Scherer P.E. The role of adipocytes and adipocyte-like cells in the severity of COVID-19 infections // Obesity (Silver Spring). 2020. Vol. 28, N 7. P. 1187-1190. DOI: 10.1002/oby.22856
35. Alexander C.M., Kasza I., Yen C.L., et al. Dermal white adipose tissue: a new component of the thermogenic response // J. Lipid Res. 2015. Vol. 56, N 11. P. 2061-2069. DOI: 10.1194/jlr.R062893
36. Byun K.A., Oh S., Son K.H., Byun K. Poly-D,L-lactic acid fillers stimulate adipogenesis by promoting the proliferation of adipose-derived stem cells in aged animal skin // Int. J. Mol. Sci. 2024. Vol. 25, N 23. P. 12739. DOI: 10.3390/ijms252312739
37. Oh S., Bae J.S., Kim K.S., et al. High-intensity focused ultrasound induces adipogenesis via control of cilia in adipose-derived stem cells in subcutaneous adipose tissue // Int. J. Mol. Sci. 2022. Vol. 23, N 16. P. 8866. DOI: 10.3390/ijms23168866
38. Sirak A.G., Grigorova A.N., Pashneva E.I., et al. Histological significance of various types of adipose tissue (literature review) // J. Volgograd State Med. Univ. 2023. Vol. 20, N 3. P. 31-36. DOI: 10.19163/1994-9480-2023-20-3-31-36
39. Романцова Т.И. Жировая ткань: цвета, депо и функции // Ожирение и метаболизм. 2021. Т. 18, № 3. С. 282-301. DOI: 10.14341/omet12743
40. Кокшарова Е.О., Деревянко О.П., Яшков Ю.И., и др. Метаболические особенности и терапевтический потенциал бурой и «бежевой» жировой ткани // Сахарный диабет. 2014. № 4. С. 5-15. DOI: 10.14341/DM2014417-15
41. Маркова Т.Н., Мищенко Н.К., Петина Д.В. Адипоцитокины: современный взгляд на дефиницию, классификацию и роль в организме // Проблемы эндокринологии. 2021. Т. 67, № 1. С. 73-80. DOI: 10.14341/probl12715
42. Sbarbati A., Accorsi D., Benati D., et al. Subcutaneous adipose tissue classification // Eur. J. Histochem. 2010. Vol. 54, N 4. P. e48. DOI: 10.4081/ejh.2010.e48
43. Chait A., den Hartigh L.J. Adipose tissue distribution, inflammation and its metabolic consequences, including diabetes and cardiovascular disease // Front. Cardiovasc. Med. 2020. Vol. 7. P. 22. DOI: 10.3389/fcvm.2020.00022
44. Byun K.A., Lee S., Oh S., et al. High-intensity focused ultrasound decreases subcutaneous fat tissue thickness by increasing apoptosis and autophagy // Biomolecules. 2023. Vol. 13, N 2. P. 392. DOI: 10.3390/biom13020392
45. Cunha M., Cunha A., Machado C.A. Hypodermis and subcutaneous adipose tissue: two different structures // Surg. Cosmet. Dermatol. 2014. Vol. 6, N 4. P. 355-359.
46. Giralt M., Villarroya F. White, brown, beige/brite: different adipose cells for different functions? // Endocrinology. 2013. Vol. 154, N 9. P. 2992-3000. DOI: 10.1210/en.2013-1403
47. Kruglikov I., Trujillo O., Kristen Q., et al. The facial adipose tissue: a revision // Facial Plast. Surg. 2016. Vol. 32, N 6. P. 671-682. DOI: 10.1055/s-0036-1596046
48. Li Y., Hu Q., Miao Z., et al. Insights into the unique roles of dermal white adipose tissue (dWAT) in wound healing // Front. Physiol. 2024. Vol. 15. P. 1349.DOI: 10.3389/fphys.2024.1349349
49. Mariman E.C.M., Wang P. Adipocyte extracellular matrix composition, dynamics and role in obesity // Cell. Mol. Life Sci. 2010. Vol. 67, N 8. P. 1277-1292. DOI: 10.1007/s00018-010-0263-4
50. Ouchi N., Parker J.L., Lugus J.J., Walsh K. Adipokines in inflammation and metabolic disease // Nat. Rev. Immunol. 2011. Vol. 11, N 2. P. 85-97. DOI: 10.1038/nri2921
51. Sepe A., Tchkonia T., Thomou T., et al. Aging and regional differences in fat cell progenitors - a mini-review // Gerontology. 2011. Vol. 57, N 1. P. 66-75. DOI: 10.1159/000279755
52. Mei R., Qin W., Zheng Y., et al. Role of adipose tissue derived exosomes in metabolic disease // Front. Endocrinol. (Lausanne). 2022. Vol. 13. P. 873865. DOI: 10.3389/fendo.2022.873865
Review
For citations:
Shirshakova M.A., Shemyakov S.E., Supil'nikov A.A., Mel'nikova Yu.E. Morphology and functional organization of subcutaneous adipose tissue: modern concepts of structural and functional heterogeneity and age-related changes (systematic literature review). Bulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH). 2025;15(3):156-164. (In Russ.) https://doi.org/10.20340/vmi-rvz.2025.3.MORPH.3