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The effect of long-chain n-3 PUFA on liver transcriptome in human obesity
Background and aims: Obesity is associated with a higher risk of severe diseases such as atherosclerotic cardiovascular disease, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD). Polyunsaturated fatty acids, of the omega-3 family (n-3 PUFA), have been shown to reduce adipose tissue inflammation in obesity, as well as to have lipid-lowering effects and improve insulin sensitivity. However, direct effects on liver transcriptome in humans have not been described. Our aim was to understand the impact of n-3 PUFA on gene expression in obese human liver. Approach and
Results: Patients with obesity (BMI ≥ 40 kg/m2) were treated for eight weeks with 3.36 g n-3 PUFAs (1.84 g eicosapentaenoic acid (EPA) and 1.53 g docosahexaenoic acid (DHA)), or with 5 g of butter as a control (n = 15 per group) before undergoing bariatric surgery where liver biopsies were taken. Liver samples were used for mRNA microarray a nalyses and subsequently Gene Set Enrichment Analysis (GSEA) was performed. This bioinformatic approach led us to identify 80 significantly dysregulated pathways that were divided into 9 different clusters including insulin and lipid metabolism, and immunity. N-3 PUFA treatment significantly affected pathways related to immunity, metabolism, and inflammation. Specifically, it upregulated pathways involved in T-cell and B-cell functions and lipid metabolism, while downregulating glucagon signalling. These findings highlight the impact of n-3 PUFAs on key metabolic and immune processes in the liver of patients with obesity.
Conclusion: This study provides further insights into the impact on n-3 PUFA on human liver gene expression, particularly in pathways associated with immunity, lipid metabolism, and inflammation, setting basis for further clinical research. Obesity increases the risk of diseases like atherosclerotic- cardiovascular disease, type 2 diabetes m ellitus and metabolic dysfunction-associated steatotic liver disease (MASLD). Omega-3 polyunsaturated fatty acids (n-3 PUFA) are known for their anti-inflammatory and metabolic benefits, but their direct impact on liver gene expression in people with obesity, remains unclear. In this study, patients with obesity (BMI ≥ 40 kg/m2) were administered either n-3 PUFAs or butter before bariatric surgery. Liver biopsies were analysed for gene expression via Gene Set Enrichment Analysis (GSEA). The results revealed 80 dysregulated pathways across 9 clusters, including those related to insulin and lipid metabolism, and immunity. This sheds light on how n-3 PUFAs influence gene expression in the liver of patients with obesity, setting the groundwork for further clinical exploration. © 2024 The Author(s)
Authors : Joerg R.; Itariu B.K.; Amor M.; Bilban M.; Langer F.; Prager G.; Joerg F.; Stulnig T.M.
Source : Churchill Livingstone
Article Information
| Year | 2025 |
| Type | Article |
| DOI | 10.1016/j.plefa.2024.102663 |
| ISSN | 09523278 |
| Volume | 204 |
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