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Updated: Jun 28, 2025
An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
Published on: May 4, 2021
Adipocyte-derived exosomes from obstructive sleep apnoea rats aggravate MASLD by TCONS_00039830/miR-455-3p/Smad2 axis
Li Yang1,2, Yan He3,4, Shijie Liu3,4
1Hypertension Center, Yan 'an Hospital of Kunming, Kunming, China. yl13330466619@163.com.
Abstract:
A correlation exists between obstructive sleep apnoea (OSA) and the severity of metabolic dysfunction-associated steatotic liver disease (MASLD), OSA can induce more severe MASLD. However, the underlying regulatory mechanism between the two is unclear. To this end, this study explored the role and possible molecular mechanisms of adipocyte-derived exosomes under OSA in aggravating MASLD. Through sequencing technology, miR-455-3p was identified as a co-differentially expressed miRNA between the MASLD + OSA and Control groups and between the MASLD + OSA and MASLD groups. Upregulation of TCONS-00039830 and Smad2 and downregulation of miR-455-3p in the MASLD and MASLD + OSA groups were validated in vivo and in vitro. TCONS-00039830, as a differentially expressed LncRNA in exosomes found in the sequencing results, transfection notably downregulated miR-455-3p and upregulated Smad2 in hepatocytes. TCONS_00039830 overexpression increased fat, triglyceride and cholesterol levels, while miR-455-3p overexpression decreased these levels. Furthermore, exosome administration promoted the accumulation of fat, triglyceride and cholesterol, upregulated TCONS_00039830 and Smad2, and downregulated miR-455-3p. Overexpression of miR-455-3p reversed the increased fat accumulation and upregulated TCONS_00039830 and Smad2. In conclusion, OSA-derived exosomes promoted hepatocyte steatosis by regulating TCONS_00039830/miR-455-3p/Smad2 axis, thereby aggravating liver damage in MASLD.
Insights
Obstructive sleep apnoea (OSA) worsens metabolic dysfunction-associated steatotic liver disease (MASLD) by promoting hepatocyte steatosis. OSA-derived exosomes regulate the TCONS-00039830/miR-455-3p/Smad2 pathway, aggravating liver damage in MASLD patients.
Area of Science:
- Hepatology
- Sleep Medicine
- Molecular Biology
Background:
- Obstructive sleep apnoea (OSA) is linked to increased severity of metabolic dysfunction-associated steatotic liver disease (MASLD).
- The precise molecular mechanisms by which OSA exacerbates MASLD remain largely undetermined.
- Adipocyte-derived exosomes are implicated in intercellular communication and may play a role in this interaction.
Purpose of the Study:
- To investigate the role of adipocyte-derived exosomes in OSA-induced MASLD aggravation.
- To elucidate the molecular mechanisms underlying the interplay between OSA and MASLD.
Main Methods:
- Exosome isolation and characterization.
- RNA sequencing to identify differentially expressed miRNAs and LncRNAs.
- In vivo and in vitro experiments using cell transfection and exosome administration.
- Validation of gene and miRNA expression levels.
Main Results:
- miR-455-3p was identified as a co-differentially expressed miRNA in MASLD+OSA versus control and MASLD groups.
- LncRNA TCONS-00039830 and Smad2 were upregulated, while miR-455-3p was downregulated in MASLD and MASLD+OSA models.
- TCONS-00039830 overexpression increased lipid accumulation; miR-455-3p overexpression reduced it.
- OSA-derived exosomes promoted steatosis via the TCONS-00039830/miR-455-3p/Smad2 axis.
Conclusions:
- Adipocyte-derived exosomes from OSA patients promote hepatocyte steatosis.
- The TCONS-00039830/miR-455-3p/Smad2 axis is a key molecular pathway mediating OSA's exacerbation of MASLD.
- Targeting this exosomal pathway may offer therapeutic strategies for MASLD.
