The Histone Deacetylase Inhibitor Sodium Butyrate Stimulates Adipogenesis Through a Limited Transcriptional Switch in Periodontal Ligament-Derived Stem Cells

Authors

  • Anahí Torres-Nájera Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Inn, Perif. de Mérida Lic. Manuel Berzunza 13615, Chuburná de Hidalgo. C.P. 97203, Mérida, Yucatán, México. Laboratorio de Células Troncales-Facultad de Odontología, Universidad Autónoma de Yucatán, Calle 61-AX Av. Itzaés Costado Sur “Parque de la Paz”, Col. Centro. C.P. 97000, Mérida, Yucatán, México. Author https://orcid.org/0009-0006-0845-0024
  • Angélica Anahí Serralta-Interían Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Inn, Perif. de Mérida Lic. Manuel Berzunza 13615, Chuburná de Hidalgo. C.P. 97203, Mérida, Yucatán, México. Laboratorio de Células Troncales-Facultad de Odontología, Universidad Autónoma de Yucatán, Calle 61-AX Av. Itzaés Costado Sur “Parque de la Paz”, Col. Centro. C.P. 97000, Mérida, Yucatán, México. Author https://orcid.org/0000-0003-2062-2141
  • Rodrigo Arturo Rivera-Solís Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Inn, Perif. de Mérida Lic. Manuel Berzunza 13615, Chuburná de Hidalgo. C.P. 97203, Mérida, Yucatán, México Author https://orcid.org/0000-0002-5721-9615
  • Geovanny Nic-Can SECIHTI-Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Periférico Norte Kilómetro 33.5, Tablaje Catastral 13615, Chuburná de Hidalgo Inn. C.P. 97203, Mérida, Yucatán, México Author https://orcid.org/0000-0001-8003-7716
  • Leydi Carrillo-Cocom Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Inn, Perif. de Mérida Lic. Manuel Berzunza 13615, Chuburná de Hidalgo. C.P. 97203, Mérida, Yucatán, México Author https://orcid.org/0000-0002-5477-7603
  • Beatriz Adriana Rodas-Junco Laboratorio de Células Troncales-Facultad de Odontología, Universidad Autónoma de Yucatán, Calle 61-AX Av. Itzaés Costado Sur “Parque de la Paz”, Col. Centro. C.P. 97000, Mérida, Yucatán, México. SECIHTI-Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Periférico Norte Kilómetro 33.5, Tablaje Catastral 13615, Chuburná de Hidalgo Inn. C.P. 97203, Mérida, Yucatán, México Author https://orcid.org/0000-0002-2804-6073

DOI:

https://doi.org/10.15517/m983tw41

Keywords:

Periodontal ligament stem cells; Histone acetylation; Adipogenesis; Histone deacetylase inhibitors.

Abstract

Adipogenic differentiation plays a crucial role in adipose tissue biology, an endocrine organ that regulates energy storage and hormone secretion. Dysfunction in this process contributes to metabolic diseases such as obesity and type II diabetes. In vitro models have been developed to investigate the mechanisms of adipogenesis, with periodontal ligament stem cells (PDLSCs) emerging as a promising model due to their multipotent capacity. Previous studies have shown that epigenetic manipulation can enhance the adipogenic response in various cell lines. Acetylation of lysine 9 on histone H3 (H3K9ac) is associated with the activation of key genes, such as PPARγ-2. In this study, we evaluated whether class I histone deacetylase inhibitors, such as valproic acid (VPA) and sodium butyrate (NaBu), both short-chain fatty acids, can increase H3K9 acetylation and influence adipogenic differentiation. We used 1, 4, and 8 mM VPA concentrations and 1, 2, and 5 mM NaBu to assess their effects on cell viability, morphology, H3K9ac distribution, and adipogenic differentiation. The results indicated that cells treated with 5 mM NaBu exhibited morphological changes, reduced viability, increased H3K9ac signal intensity, and enhanced intracellular lipid deposition. These results infer that inhibition of HDACs by NaBu increases plasticity toward adipogenesis of PDLSCs through a limited transcriptional change in their key genes.

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Published

2025-08-27