Effects of obesity-associated plasma markers on adipose stem cell function and epigenetic regulation

Author(s)

Bispo, Andressa Franca Sousa ; Simao, Jussara de Jesus ; Moraes, Miguel Ambrizzi ; Abel, Ana Beatriz Marques ; Plata, Victor Tadeu Goncalves ; Telles, Monica Marques ; Santana, Andre Valente ; Volpe, Paula ; Armelin-Correa, Lucia Maria ; Alonso-Vale, Maria Isabel Cardoso

• Document type: Journal article
• Source: OBESITY; v. N/A, p. 14-pg., 2025-06-16.

Abstract

ObjectiveThis study investigates the correlations between obesity-related plasma markers and epigenetic/inflammatory changes in white adipose tissue (WAT), focusing on adipose-derived stem cells (ASCs). We hypothesize that obesity modulates histone H3K27 marks, modified by demethylases (lysine-specific demethylase 6A and 6B [KDM6A/KDM6B]) and acetylases (CREB-binding protein [CREBBP]/histone acetyltransferase EP300), affecting ASC function.MethodsSerum and visceral WAT (omental region) was collected from male patients (n = 16, 30-50 years old) undergoing elective gastric or bariatric surgery. BMI and obesity markers were correlated with changes in ASCs (transcript expression, proliferation, and secretion) using reverse transcriptase-polymerase chain reaction.ResultsASCs from individuals with higher BMI exhibited slower proliferation, increased inflammatory profile, and reduced adipogenic potential, with lower expression of key adipogenic genes. H3K27 acetylase transcripts were also negatively correlated with adipogenesis regulators. Moreover, C-C motif chemokine 2 (CCL2) and KDM6A expression was higher in the group with obesity, as were CREBBP and EP300. Finally, leptin levels positively correlated with serum, WAT, and ASC CCL2 expression. In vitro, leptin exposure enhanced CCL2 expression/secretion and increased KDM6A/KDM6B and EP300 transcription.ConclusionsIn vitro leptin exposure enhanced CCL2 expression/secretion and increased KDM6A/KDM6B and EP300 transcription, highlighting how obesity-driven epigenetic mechanisms, including leptin-mediated pathways, disrupt ASC plasticity and perpetuate adipose tissue dysfunction, offering novel therapeutic targets for metabolic disease intervention. (AU)

• FAPESP's process: 23/18371-7 - Deposition of epigenetic marks on lysine 27 of histone 3 (H3K27) in mesenchymal stem cells derived from human adipose tissue with obesity.
• Grantee: Miguel Ambrizzi Moraes
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/15127-5 - Modulation of NF-kB signaling pathway and repercussions on epigenetic marks in adipose cells: role of Oncotherad®
• Grantee: Andressa Franca de Sousa Bispo
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/26240-4 - Signaling pathways affected by fish oil in Adipose tissue-Derived Stem Cells (AdSCs) and adipocytes: correlation with metabolic, endocrine and adipogenic changes that impact its anti-Hypertrophic Obesity properties
• Grantee: Jussara de Jesus Simão
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/13618-9 - Modulation of Ezh2 expression, and other H3K27 modifiers, by NF-kB transcription factors in adipose cells
• Grantee: Maria Isabel Cardoso Alonso-Vale
• Support Opportunities: Regular Research Grants