Poly-D,L-Lactic Acid Fillers Increase Subcutaneous Adipose Tissue Volume by Promoting Adipogenesis in Aged Animal Skin

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Dec 17

PMID 39684448

Authors

Kyung-A Byun

Suk Bae Seo

Seyeon Oh

Jong-Won Jang

Kuk Hui Son

Kyunghee Byun

Affiliations

Soon will be listed here.

Abstract

During aging, subcutaneous white adipose tissue (sWAT) thickness and the adipogenic potential of adipose-derived stem cells (ASCs) decline. Poly-D,L-lactic acid (PDLLA) fillers are commonly used to restore diminished facial volume. Piezo1 increases polarizing macrophages towards the M2 phenotype, which promotes the secretion of fibroblast growth factor 2 (FGF2), thereby increasing ASC survival. This study evaluated whether PDLLA enhances adipogenesis in ASCs by modulating M2 polarization in an in vitro senescence model and in aged animals. Lipopolysaccharide (LPS)-induced senescent macrophages showed decreased Piezo1, which was upregulated by PDLLA. CD163 (an M2 marker) and FGF2 were downregulated in senescent macrophages but were upregulated by PDLLA. We evaluated whether reduced FGF2 secretion from senescent macrophages affects ASCs by applying conditioned media (CM) from macrophage cultures to ASCs. CM from senescent macrophages decreased ERK1/2 and proliferation in ASCs, both of which were restored by CM from PDLLA-stimulated senescent macrophages. Adipogenesis inducers (PPAR-γ and C/EBP-α) were downregulated by CM from senescent macrophages but upregulated by CM from PDLLA-stimulated senescent macrophages in ASCs. Similar patterns were observed in aged animal adipose tissue. PDLLA increased Piezo1 activity, M2 polarization, and FGF2 levels. PDLLA also enhanced ERK1/2, cell proliferation, PPAR-γ, and C/EBP-α expression, leading to increased adipose tissue thickness. In conclusion, our study showed that PDLLA increased adipose tissue thickness by modulating adipogenesis.

Citing Articles

Temporal Fat Pad Filler Injection for Lifting Purposes: Shifting of the Superficial Layer of Deep Temporal Fascia.

Yi K, Wan J, Kim S, Kim H J Cosmet Dermatol. 2025; 24(3):e70023.

PMID: 40000367 PMC: 11859875. DOI: 10.1111/jocd.70023.

References

Horiba S, Kawamoto M, Tobita R, Kami R, Ogura Y, Hosoi J . M1/M2 Macrophage Skewing is Related to Reduction in Types I, V, and VI Collagens with Aging in Sun-Exposed Human Skin. JID Innov. 2023; 3(6):100222. PMC: 10542643. DOI: 10.1016/j.xjidi.2023.100222. View

Padwal R, Sharma A . Prevention of cardiovascular disease: obesity, diabetes and the metabolic syndrome. Can J Cardiol. 2010; 26 Suppl C:18C-20C. PMC: 2949982. DOI: 10.1016/s0828-282x(10)71077-1. View

Fong C, Bebien M, Didierlaurent A, Nebauer R, Hussell T, Broide D . An antiinflammatory role for IKKbeta through the inhibition of "classical" macrophage activation. J Exp Med. 2008; 205(6):1269-76. PMC: 2413025. DOI: 10.1084/jem.20080124. View

Nirwan R, Albini T, Sridhar J, Flynn Jr H, Kuriyan A . Assessing "Cell Therapy" Clinics Offering Treatments of Ocular Conditions using Direct-to-Consumer Marketing Websites in the United States. Ophthalmology. 2019; 126(10):1350-1355. PMC: 6754792. DOI: 10.1016/j.ophtha.2019.03.019. View

Niemann B, Simm A, Rohrbach S . Mechanisms Involved in Premature Aging in the Heart-Is There an Implication for Cardiac Surgery?. Thorac Cardiovasc Surg. 2017; 66(1):31-41. DOI: 10.1055/s-0037-1607052. View

Hasegawa K, Fujii S, Matsumoto S, Tajiri Y, Kikuchi A, Kiyoshima T . YAP signaling induces PIEZO1 to promote oral squamous cell carcinoma cell proliferation. J Pathol. 2020; 253(1):80-93. DOI: 10.1002/path.5553. View

Li W, Pappas A, Zhang L, Ruvolo E, Cavender D . IL-11, IL-1α, IL-6, and TNF-α are induced by solar radiation in vitro and may be involved in facial subcutaneous fat loss in vivo. J Dermatol Sci. 2013; 71(1):58-66. DOI: 10.1016/j.jdermsci.2013.03.009. View

Li Y, Xu C, Sun B, Zhong F, Cao M, Yang L . Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c. Cancer Cell Int. 2022; 22(1):162. PMC: 9035260. DOI: 10.1186/s12935-022-02574-2. View

Ho C, Dreesen O . Faces of cellular senescence in skin aging. Mech Ageing Dev. 2021; 198:111525. DOI: 10.1016/j.mad.2021.111525. View

10.

Schipper B, Marra K, Zhang W, Donnenberg A, Rubin J . Regional anatomic and age effects on cell function of human adipose-derived stem cells. Ann Plast Surg. 2008; 60(5):538-44. PMC: 4160894. DOI: 10.1097/SAP.0b013e3181723bbe. View

11.

Patel N, Kumar S, Eggo M . Essential role of fibroblast growth factor signaling in preadipoctye differentiation. J Clin Endocrinol Metab. 2004; 90(2):1226-32. DOI: 10.1210/jc.2004-1309. View

12.

Kruglikov I, Scherer P . Dermal Adipocytes: From Irrelevance to Metabolic Targets?. Trends Endocrinol Metab. 2015; 27(1):1-10. PMC: 4698208. DOI: 10.1016/j.tem.2015.11.002. View

13.

Wang H, Fu H, Zhu R, Wu X, Ji X, Li X . BRD4 contributes to LPS-induced macrophage senescence and promotes progression of atherosclerosis-associated lipid uptake. Aging (Albany NY). 2020; 12(10):9240-9259. PMC: 7288959. DOI: 10.18632/aging.103200. View

14.

Skurk T, Alberti-Huber C, Herder C, Hauner H . Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2006; 92(3):1023-33. DOI: 10.1210/jc.2006-1055. View

15.

Wilson C, Clegg R, Leavesley D, Pearcy M . Mediation of biomaterial-cell interactions by adsorbed proteins: a review. Tissue Eng. 2005; 11(1-2):1-18. DOI: 10.1089/ten.2005.11.1. View

16.

Donato A, Henson G, Hart C, Layec G, Trinity J, Bramwell R . The impact of ageing on adipose structure, function and vasculature in the B6D2F1 mouse: evidence of significant multisystem dysfunction. J Physiol. 2014; 592(18):4083-96. PMC: 4198016. DOI: 10.1113/jphysiol.2014.274175. View

17.

Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N . IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol. 2011; 12(3):231-8. DOI: 10.1038/ni.1990. View

18.

Horiba S, Kami R, Tsutsui T, Hosoi J . IL-34 Downregulation‒Associated M1/M2 Macrophage Imbalance Is Related to Inflammaging in Sun-Exposed Human Skin. JID Innov. 2022; 2(3):100112. PMC: 9062483. DOI: 10.1016/j.xjidi.2022.100112. View

19.

Kim S, Lun M, Wang M, Senyo S, Guillermier C, Patwari P . Loss of white adipose hyperplastic potential is associated with enhanced susceptibility to insulin resistance. Cell Metab. 2014; 20(6):1049-58. PMC: 4715375. DOI: 10.1016/j.cmet.2014.10.010. View

20.

Wynes M, Frankel S, Riches D . IL-4-induced macrophage-derived IGF-I protects myofibroblasts from apoptosis following growth factor withdrawal. J Leukoc Biol. 2004; 76(5):1019-27. DOI: 10.1189/jlb.0504288. View