Cationic Polymer Effect on Brown Adipogenic Induction of Dedifferentiated Fat Cells

Overview

Journal Mater Today Bio

Specialty Biomedical Engineering

Date 2024 Aug 8

PMID 39113911

Authors

Asli Sena Karanfil

Fiona Louis

Yoshihiro Sowa

Michiya Matsusaki

Affiliations

Soon will be listed here.

Abstract

Obesity and its associated comorbidities place a substantial burden on public health. Given the considerable potential of brown adipose tissue in addressing metabolic disorders that contribute to dysregulation of the body's energy balance, this area is an intriguing avenue for research. This study aimed to assess the impact of various polymers, including collagen type I, fibronectin, laminin, gelatin, gellan gum, and poly-l-lysine (PLL), on the brown adipogenic differentiation of dedifferentiated fat cells within a fibrin gel matrix. The findings, obtained through RT-qPCR, immunofluorescent imaging, ELISA assay, and mitochondria assessment, revealed that PLL exhibited a significant browning-inducing effect. Compared to fibrin-only brown-like drops after two weeks of incubation in brown adipogenic medium, PLL showed 6 (±3) times higher UCP1 gene expression, 5 (±2) times higher UCP1 concentration by ELISA assay, and 2 (±1) times higher mitochondrial content. This effect can be attributed to PLL's electrostatic properties, which potentially facilitate the cellular uptake of crucial brown adipogenic inducers such as the thyroid hormone, triiodothyronine (T3), and insulin from the induction medium.

References

Karanfil A, Louis F, Sowa Y, Matsusaki M . ECM proteins and cationic polymers coating promote dedifferentiation of patient-derived mature adipocytes to stem cells. Biomater Sci. 2023; 11(23):7623-7638. DOI: 10.1039/d3bm00934c. View

Carobbio S, Guenantin A, Bahri M, Rodriguez-Fdez S, Honig F, Kamzolas I . Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue. Stem Cell Reports. 2021; 16(3):641-655. PMC: 7940445. DOI: 10.1016/j.stemcr.2021.01.013. View

Choudhery M, Badowski M, Muise A, Pierce J, Harris D . Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. J Transl Med. 2014; 12:8. PMC: 3895760. DOI: 10.1186/1479-5876-12-8. View

Hammel J, Bellas E . Endothelial cell crosstalk improves browning but hinders white adipocyte maturation in 3D engineered adipose tissue. Integr Biol (Camb). 2020; 12(4):81-89. PMC: 7167464. DOI: 10.1093/intbio/zyaa006. View

Antillon D, Towfighi A . No time to 'weight': the link between obesity and stroke in women. Womens Health (Lond). 2011; 7(4):453-63. DOI: 10.2217/whe.11.36. View

Maurer S, Harms M, Boucher J . The colorful versatility of adipocytes: white-to-brown transdifferentiation and its therapeutic potential in humans. FEBS J. 2020; 288(12):3628-3646. DOI: 10.1111/febs.15470. View

Wittmann K, Dietl S, Ludwig N, Berberich O, Hoefner C, Storck K . Engineering vascularized adipose tissue using the stromal-vascular fraction and fibrin hydrogels. Tissue Eng Part A. 2015; 21(7-8):1343-53. DOI: 10.1089/ten.TEA.2014.0299. View

Horinouchi C, Barison M, Robert A, Kuligovski C, Aguiar A, Dallagiovanna B . Influence of donor age on the differentiation and division capacity of human adipose-derived stem cells. World J Stem Cells. 2021; 12(12):1640-1651. PMC: 7789122. DOI: 10.4252/wjsc.v12.i12.1640. View

Chouchani E, Kazak L, Spiegelman B . New Advances in Adaptive Thermogenesis: UCP1 and Beyond. Cell Metab. 2018; 29(1):27-37. DOI: 10.1016/j.cmet.2018.11.002. View

10.

Tharp K, Jha A, Kraiczy J, Yesian A, Karateev G, Sinisi R . Matrix-Assisted Transplantation of Functional Beige Adipose Tissue. Diabetes. 2015; 64(11):3713-24. PMC: 4613967. DOI: 10.2337/db15-0728. View

11.

Shapira S, Seale P . Transcriptional Control of Brown and Beige Fat Development and Function. Obesity (Silver Spring). 2018; 27(1):13-21. PMC: 6309799. DOI: 10.1002/oby.22334. View

12.

Jumabay M, Bostrom K . Dedifferentiated fat cells: A cell source for regenerative medicine. World J Stem Cells. 2015; 7(10):1202-14. PMC: 4663373. DOI: 10.4252/wjsc.v7.i10.1202. View

13.

Scully T, Ettela A, LeRoith D, Gallagher E . Obesity, Type 2 Diabetes, and Cancer Risk. Front Oncol. 2021; 10:615375. PMC: 7884814. DOI: 10.3389/fonc.2020.615375. View

14.

Hemmrich K, von Heimburg D . Biomaterials for adipose tissue engineering. Expert Rev Med Devices. 2006; 3(5):635-45. DOI: 10.1586/17434440.3.5.635. View

15.

Zhang N, Kohn D . Using polymeric materials to control stem cell behavior for tissue regeneration. Birth Defects Res C Embryo Today. 2012; 96(1):63-81. PMC: 5538808. DOI: 10.1002/bdrc.21003. View

16.

Gonzalez Porras M, Stojkova K, Vaicik M, Pelowe A, Goddi A, Carmona A . Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity. Sci Rep. 2021; 11(1):5442. PMC: 7940610. DOI: 10.1038/s41598-021-84828-z. View

17.

Murphy C, Liaw L, Reagan M . tissue-engineered adipose constructs for modeling disease. BMC Biomed Eng. 2020; 1. PMC: 7055683. DOI: 10.1186/s42490-019-0027-7. View

18.

Kawazoe N, Guo L, Wozniak M, Imaizumi Y, Tateishi T, Zhang X . Adipogenic differentiation of mesenchymal stem cells on micropatterned polyelectrolyte surfaces. J Nanosci Nanotechnol. 2009; 9(1):230-9. DOI: 10.1166/jnn.2009.j003. View

19.

Wu J, Bostrom P, Sparks L, Ye L, Choi J, Giang A . Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012; 150(2):366-76. PMC: 3402601. DOI: 10.1016/j.cell.2012.05.016. View

20.

Naumenko E, Akhatova F, Rozhina E, Fakhrullin R . Revisiting the Cytotoxicity of Cationic Polyelectrolytes as a Principal Component in Layer-by-Layer Assembly Fabrication. Pharmaceutics. 2021; 13(8). PMC: 8400787. DOI: 10.3390/pharmaceutics13081230. View