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Review
. 2025 May 28;17(11):1836.
doi: 10.3390/nu17111836.

Dietary Omega-3 PUFAs in Metabolic Disease Research: A Decade of Omics-Enabled Insights (2014-2024)

Jing Li  1   2   3 , Yang-Chi-Dung Lin  1   2   3 , Hua-Li Zuo  1   2   3 , Hsi-Yuan Huang  1   2   3 , Tao Zhang  4 , Jin-Wei Bai  2 , Hsien-Da Huang  1   2   3   5
Affiliations
Review

Dietary Omega-3 PUFAs in Metabolic Disease Research: A Decade of Omics-Enabled Insights (2014-2024)

Jing Li et al. Nutrients. .

Abstract

Background/Objectives: The rising global prevalence of metabolic diseases (e.g., obesity, type 2 diabetes mellitus) underscores the need for effective interventions. Omega-3 polyunsaturated fatty acids (PUFAs) exhibit therapeutic potential, yet their molecular mechanisms remain unclear. This systematic review synthesizes a decade (2014-2024) of omics research to elucidate Omega-3 PUFA mechanisms in metabolic diseases and identify future directions. Methods: A PRISMA-guided search of the Web of Science identified studies on Omega-3 PUFAs, metabolic diseases, and omics. After excluding reviews, non-English articles, and irrelevant studies, 72 articles were analyzed (16 multi-omics, 17 lipidomics, 10 transcriptomics/metabolomics/microbiomics each, and 6 proteomics). Results: Omics studies demonstrated that Omega-3 PUFAs, particularly EPA and DHA, improve metabolic health through interconnected mechanisms. They regulate epigenetic processes, including DNA methylation and miRNA expression, influencing genes linked to inflammation and insulin sensitivity. Omega-3 PUFAs reduce oxidative stress by mitigating protein carbonylation and enhancing antioxidant defenses. Gut microbiota modulation is evident through increased beneficial taxa (e.g., Bacteroidetes, Akkermansia) and reduced pro-inflammatory species, correlating with improved metabolic parameters. Mitochondrial function is enhanced via upregulated fatty acid oxidation and TCA cycle activity, while anti-inflammatory effects arise from NF-κB pathway suppression and macrophage polarization toward an M2 phenotype. Challenges include interindividual variability in responses and a limited understanding of dynamic metabolic interactions. Conclusions: Omega-3 PUFAs target multiple pathways to improve metabolic health. Future research should prioritize chemoproteomics for direct target identification, multi-omics integration, and personalized strategies combining Omega-3 with therapies like calorie restriction.

Keywords: metabolic diseases; omega-3 polyunsaturated fatty acids; omics.

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Conflict of interest statement

Author T. Z. was employed by the company Better Way (Shanghai) Cosmetics Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Trends in the five countries with the highest absolute burden of five metabolic diseases, 1990–2021 (Based on DALYs and mortality data).
Figure 2
Figure 2
Polyunsaturated fatty acids and dietary sources. (a) Chemical structure and dietary sources; (b) general metabolic pathway for Omega-3 and Omega-6 PUFAs.
Figure 3
Figure 3
PRISMA flowchart of study inclusion and exclusion and distribution of publication numbers by omic types for included studies. (a) Eligibility criteria for the selection of research articles. (b) Distribution of publication numbers by omic types for the 72 included studies.
Figure 4
Figure 4
Geographical distribution of omics-based research publications on Omega-3 PUFAs in animal or human models (ranked by publication volume by country).
Figure 5
Figure 5
Mechanistic insights into Omega-3 PUFAs in metabolic diseases through omics analysis in animal and human models.
See this image and copyright information in PMC

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