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A Study on the Acquisition and Identification of Beige Adipocytes and Exosomes as Well as Their Inflammatory Regulation by Promoting Macrophage Polarization

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  • Basic Science/Experimental
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Aesthetic Plastic Surgery Aims and scope Submit manuscript

Abstract

Background

The fat retention rate is associated with postoperative inflammation. However, fat survival is still unpredictable even when supplemented with adipose-derived stem cells (ADSCs). Beige adipocytes play a role in regulating pathological inflammation. Thus, we assumed that exosomes may promote macrophage polarization to regulate inflammation when we simulated postgrafted inflammation by lipopolysaccharide (LPS) induction.

Methods

3T3-L1 preadipocytes were used to differentiate into beige adipocytes, which were stimulated by special culture media, and then, exosomes were isolated from the supernatant. We identified them by morphology, protein and gene expression, or size distribution. Next, we utilized exosomes to stimulate LPS-induced macrophages and evaluated the changes in inflammatory cytokines and macrophage polarization.

Results

The induced cells contained multilocular lipid droplets and expressed uncoupling protein 1 (UCP1) and beige adipocyte-specific gene. The exosomes, which were approximately 111.5 nm and cup-like, were positive for surface markers. Additionally, the levels of proinflammatory-related indicators in the LPS+exosomes (LPS+Exos) group were increased after inflammation was activated for 6 h. When inflammation lasted 16 h, exosomes decreased the expression of proinflammatory-related indicators and increased the expression of anti-inflammatory-related indicators compared with the group without exosomes.

Conclusion

The method described in this article can successfully obtain beige adipocytes and exosomes. The results suggest that beige adipocyte exosomes can promote inflammatory infiltration and polarize more macrophages to the M1 type in the early period of inflammation, accelerating the occurrence of the inflammation endpoint and the progression of macrophage switching from M1 to M2, while inflammation develops continuously.

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References

  1. Cohen P, Kajimura S (2021) The cellular and functional complexity of thermogenic fat. Nat Rev Mol Cell Biol 22:393–409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hasegawa Y, Ikeda K, Chen Y, Alba DL, Stifler D, Shinoda K, Hosono T, Maretich P, Yang Y, Ishigaki Y, Chi J, Cohen P, Koliwad SK, Kajimura S (2018) Repression of adipose tissue fibrosis through a PRDM16-GTF2IRD1 complex improves systemic glucose homeostasis. Cell Metab 27(180–194):e186

    Google Scholar 

  3. Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ, Wu J, Gunawardana SC, Banks AS, Camporez JP, Jurczak MJ, Kajimura S, Piston DW, Mathis D, Cinti S, Shulman GI, Seale P, Spiegelman BM (2014) Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156:304–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhao H, Shang Q, Pan Z, Bai Y, Li Z, Zhang H, Zhang Q, Guo C, Zhang L, Wang Q (2018) Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue. Diabetes 67:235–247

    Article  CAS  PubMed  Google Scholar 

  5. Guo DH, Yamamoto M, Hernandez CM, Khodadadi H, Baban B, Stranahan AM (2021) Beige adipocytes mediate the neuroprotective and anti-inflammatory effects of subcutaneous fat in obese mice. Nat Commun 12:4623

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mills EL, Harmon C, Jedrychowski MP, Xiao H, Garrity R, Tran NV, Bradshaw GA, Fu A, Szpyt J, Reddy A, Prendeville H, Danial NN, Gygi SP, Lynch L, Chouchani ET (2021) UCP1 governs liver extracellular succinate and inflammatory pathogenesis. Nat Metab 3:604–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Oguri Y, Shinoda K, Kim H, Alba DL, Bolus WR, Wang Q, Brown Z, Pradhan RN, Tajima K, Yoneshiro T, Ikeda K, Chen Y, Cheang RT, Tsujino K, Kim CR, Greiner VJ, Datta R, Yang CD, Atabai K, McManus MT, Koliwad SK, Spiegelman BM, Kajimura S (2020) CD81 controls beige fat progenitor cell growth and energy balance via FAK signaling. Cell 182(563–577):e520

    Google Scholar 

  8. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerback S, Schrauwen P, Spiegelman BM (2012) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Finlin BS, Memetimin H, Confides AL, Kasza I, Zhu B, Vekaria HJ, Harfmann B, Jones KA, Johnson ZR, Westgate PM, Alexander CM, Sullivan PG, Dupont-Versteegden EE, Kern PA (2018) Human adipose beiging in response to cold and mirabegron. JCI Insight 3(15)

  10. La Padula S, Ponzo M, Lombardi M, Iazzetta V, Errico C, Polverino G, Pensato R (2023) Nanofat in plastic reconstructive, regenerative, and aesthetic surgery: a review of advancements in face-focused applications. J Clin Med 12(13):4351

    Article  PubMed  PubMed Central  Google Scholar 

  11. Groen JW, Negenborn VL, Twisk JW, Ket JC, Mullender MG, Smit JM (2016) Autologous fat grafting in cosmetic breast augmentation: a systematic review on radiological safety, complications, volume retention, and patient/surgeon satisfaction. Aesthet Surg J 36:993–1007

    Article  PubMed  Google Scholar 

  12. Mok H, Feng J, Hu W, Wang J, Cai J, Lu F (2018) Decreased serum estrogen improves fat graft retention by enhancing early macrophage infiltration and inducing adipocyte hypertrophy. Biochem Biophys Res Commun 501:266–272

    Article  CAS  PubMed  Google Scholar 

  13. Li Y, Mou S, Xiao P, Li G, Li J, Tong J, Wang J, Yang J, Sun J, Wang Z (2020) Delayed two steps PRP injection strategy for the improvement of fat graft survival with superior angiogenesis. Sci Rep 10:5231

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang Y, Cai J, Zhou T, Yao Y, Dong Z, Lu F (2018) Improved long-term volume retention of stromal vascular fraction gel grafting with enhanced angiogenesis and adipogenesis. Plast Reconstr Surg 141:676e–686e

    Article  CAS  PubMed  Google Scholar 

  15. Haarer J, Johnson CL, Soeder Y, Dahlke MH (2015) Caveats of mesenchymal stem cell therapy in solid organ transplantation. Transpl Int 28:1–9

    Article  PubMed  Google Scholar 

  16. Yu M, Gai C, Li Z, Ding D, Zheng J, Zhang W, Lv S, Li W (2019) Targeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells. Cancer Sci 110:3173–3182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kalluri R, LeBleu VS (2020) The biology, function, and biomedical applications of exosomes. Science 367(6478):eaau6977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ikeda K, Yamada T (2020) UCP1 dependent and independent thermogenesis in brown and beige adipocytes. Front Endocrinol (Lausanne) 11:498

    Article  PubMed  Google Scholar 

  19. Ikeda K, Maretich P, Kajimura S (2018) The common and distinct features of brown and beige adipocytes. Trends Endocrinol Metab 29:191–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang W, Seale P (2016) Control of brown and beige fat development. Nat Rev Mol Cell Biol 17:691–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jablonski KA, Amici SA, Webb LM, Ruiz-Rosado Jde D, Popovich PG, Partida-Sanchez S, Guerau-de-Arellano M (2015) Novel markers to delineate murine M1 and M2 macrophages. PLoS ONE 10:e0145342

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lv R, Bao Q, Li Y (2017) Regulation of M1-type and M2-type macrophage polarization in RAW264.7 cells by galectin-9. Mol Med Rep 16:9111–9119

    Article  CAS  PubMed  Google Scholar 

  23. Li G, Xie C, Lu S, Nichols RG, Tian Y, Li L, Patel D, Ma Y, Brocker CN, Yan T, Krausz KW, Xiang R, Gavrilova O, Patterson AD, Gonzalez FJ (2017) Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota. Cell Metab 26(672–685):e674

    Google Scholar 

  24. Park J, Kim M, Sun K, An YA, Gu X, Scherer PE (2017) VEGF-A–expressing adipose tissue shows rapid beiging and enhanced survival after transplantation and confers IL-4–independent metabolic improvements. Diabetes 66(6):1479–1490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xu Y, Wang N, Tan HY, Li S, Zhang C, Zhang Z, Feng Y (2020) Panax notoginseng saponins modulate the gut microbiota to promote thermogenesis and beige adipocyte reconstruction via leptin-mediated AMPKalpha/STAT3 signaling in diet-induced obesity. Theranostics 10:11302–11323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Scheja L, Heeren J (2019) The endocrine function of adipose tissues in health and cardiometabolic disease. Nat Rev Endocrinol 15:507–524

    Article  CAS  PubMed  Google Scholar 

  27. Guo L, Zhang P, Chen Z, Xia H, Li S, Zhang Y, Kobberup S, Zou W, Lin JD (2017) Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression. J Clin Invest 127:4449–4461

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bae YC, Kim KH, Yun HJ, Oh CH, Chang JH, Yi CR, Lee JW, Bae SH (2020) A study on the effective ratio of fat to stromal vascular fraction for cell-assisted lipotransfer. Aesthet Plast Surg 44:162–167

    Article  Google Scholar 

  29. Ho CK, Zheng D, Sun J, Wen D, Wu S, Yu L, Li Q (2022) LRG-1 promotes fat graft survival through the RAB31-mediated inhibition of hypoxia-induced apoptosis. J Cell Mol Med 26(11):3153–3168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kato H, Mineda K, Eto H, Doi K, Kuno S, Kinoshita K, Kanayama K, Yoshimura K (2014) Degeneration, regeneration, and cicatrization after fat grafting: dynamic total tissue remodeling during the first 3 months. Plast Reconstr Surg 133:303e–313e

    Article  CAS  PubMed  Google Scholar 

  31. Jetten N, Verbruggen S, Gijbels MJ, Post MJ, De Winther MP, Donners MM (2014) Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo. Angiogenesis 17:109–118

    Article  CAS  PubMed  Google Scholar 

  32. Kordelas L, Rebmann V, Ludwig AK, Radtke S, Ruesing J, Doeppner TR, Epple M, Horn PA, Beelen DW, Giebel B (2014) MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease. Leukemia 28:970–973

    Article  CAS  PubMed  Google Scholar 

  33. Chen B, Cai J, Wei Y, Jiang Z, Desjardins HE, Adams AE, Li S, Kao HK, Guo L (2019) Exosomes are comparable to source adipose stem cells in fat graft retention with up-regulating early inflammation and angiogenesis. Plast Reconstr Surg 144:816e–827e

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to sincerely thank our partners for their valuable comments on the design and performance of this study.

Funding

The funding was provided by Zhejiang Provincial Natural Science Foundation of China, (Grant No. LY23H150002), Chichi Li. Wenzhou City Science and Technology Foundation, (Grant No. Y20190116), Chichi Li

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Authors and Affiliations

  1. Department of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, 325000, People’s Republic of China

    Binsha Wu, Tianyu Wang, Junyan Wei & Chichi Li

  2. Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, 325000, People’s Republic of China

    Wei Cen

  3. Department of Plastic Surgery, Lishui Central Hospital, Wanxiang, Lishui City, Zhejiang Province, 323000, People’s Republic of China

    Chi Liu

  4. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, 325000, People’s Republic of China

    Shiqi Wang & Dan Zhang

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  1. Binsha Wu
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Contributions

BW and WC contributed equally to this work. BW, CL and DZ contributed to the study conception and design. BW, CL and TW performed the experiments, and all authors contributed to data analysis. BW and CL wrote the paper, and all authors checked the final manuscript. BW and WC revise the paper, and all authors checked the final manuscript.

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Correspondence to Dan Zhang or Chichi Li.

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Wu, B., Cen, W., Liu, C. et al. A Study on the Acquisition and Identification of Beige Adipocytes and Exosomes as Well as Their Inflammatory Regulation by Promoting Macrophage Polarization. Aesth Plast Surg 48, 519–529 (2024). https://doi.org/10.1007/s00266-023-03782-5

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