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Published on: May 4, 2021
MicroRNA Profiling in Adipose Before and After Weight Loss Highlights the Role of miR-223-3p and the NLRP3
Donia Macartney-Coxson1, Kirsty Danielson2, Jane Clapham1
1Human Genomics, Institute of Environmental Science and Research (ESR), Wellington, New Zealand.
Objective:
Adipose tissue plays a key role in obesity-related metabolic dysfunction. MicroRNA (miRNA) are gene regulatory molecules involved in intercellular and inter-organ communication. It was hypothesized that miRNA levels in adipose tissue would change after gastric bypass surgery and that this would provide insights into their role in obesity-induced metabolic dysregulation.
Methods:
miRNA profiling (Affymetrix GeneChip miRNA 2.0 Array) of omental and subcutaneous adipose (n = 15 females) before and after gastric bypass surgery was performed.
Results:
One omental and thirteen subcutaneous adipose miRNAs were significantly differentially expressed after gastric bypass, including downregulation of miR-223-3p and its antisense relative miR-223-5p in both adipose tissues. mRNA levels of miR-223-3p targets NLRP3 and GLUT4 were decreased and increased, respectively, following gastric bypass in both adipose tissues. Significantly more NLRP3 protein was observed in omental adipose after gastric bypass (P = 0.02). Significant hypomethlyation of NLRP3 and hypermethylation of miR-223 were observed in both adipose tissues after gastric bypass. In subcutaneous adipose, significant correlations were observed between both miR-223-3p and miR-223-5p and glucose and between NLRP3 mRNA and protein levels and blood lipids.
Conclusions:
This is the first report detailing genome-wide miRNA profiling of omental adipose before and after gastric bypass, and it further highlights the association of miR-223-3p and the NLRP3 inflammasome with obesity.
Insights
Gastric bypass surgery altered microRNA (miRNA) levels in adipose tissue, impacting genes related to obesity and metabolism. This study reveals changes in miR-223 and NLRP3, offering insights into metabolic regulation.
Area of Science:
- Metabolic Surgery
- Molecular Biology
- Obesity Research
Background:
- Adipose tissue is crucial in obesity-related metabolic dysfunction.
- MicroRNAs (miRNAs) are key regulators in cell and organ communication.
- Gastric bypass surgery is a significant intervention for obesity.
Purpose of the Study:
- To investigate changes in miRNA levels in adipose tissue after gastric bypass surgery.
- To understand the role of these miRNAs in obesity-induced metabolic dysregulation.
- To provide genome-wide miRNA profiling of omental adipose tissue post-surgery.
Main Methods:
- Omental and subcutaneous adipose tissue samples were collected from 15 female participants before and after gastric bypass.
- MicroRNA profiling was performed using Affymetrix GeneChip miRNA 2.0 Array.
- Analysis included mRNA and protein levels, methylation status, and correlations with metabolic markers.
Main Results:
- Differential expression of 14 miRNAs, including downregulation of miR-223-3p and miR-223-5p, was observed in adipose tissue.
- Changes in mRNA levels of miR-223 targets (NLRP3, GLUT4) and increased NLRP3 protein in omental adipose were noted.
- Correlations between miR-223, NLRP3, glucose, and blood lipids were found in subcutaneous adipose tissue.
Conclusions:
- This study is the first to provide genome-wide miRNA profiling of omental adipose tissue before and after gastric bypass.
- The findings highlight the association between miR-223, the NLRP3 inflammasome, and obesity.
- Adipose tissue miRNA alterations post-gastric bypass offer insights into improved metabolic health.
